Stochastic demethylation and redundant epigenetic suppressive mechanisms generate highly heterogeneous responses to pharmacological DNA methyltransferase inhibition.

Background: Despite promising preclinical studies, the application of DNA methyltransferase inhibitors in treating patients with solid cancers has thus far produced only modest outcomes. The presence of intratumoral heterogeneity in response to DNA methyltransferase inhibitors could significantly influence clinical efficacy, yet our understanding of the single-cell response to these drugs in solid tumors remains very limited.

Methods: In this study, we used cancer/testis antigen genes as a model for methylation-dependent gene expression to examine the activity of DNA methyltransferase inhibitors and their potential synergistic effect with histone deacetylase inhibitors at the single-cancer cell level.

Internal mammary node irradiation in 4541 node-positive breast cancer patients treated with newer systemic therapies and 3D-based radiotherapy (DBCG IMN2): a prospective, nationwide, population-based cohort study.

Background: Internal mammary node irradiation (IMNI) improves overall survival (OS) in node-positive breast cancer patients. However, the effect is not documented in breast cancer patients treated with newer systemic therapies and 3D-based radiotherapy (RT). Therefore, the Danish Breast Cancer Group (DBCG) IMN2 study aimed to investigate the effect of IMNI in node-positive breast cancer patients treated with newer systemic therapies and 3D-based RT.

Design and in vitro anticancer assessment of a click chemistry-derived dinuclear copper artificial metallo-nuclease.

Copper compounds with artificial metallo-nuclease (AMN) activity are mechanistically unique compared to established metallodrugs. Here, we describe the development of a new dinuclear copper AMN, Cu2-BPL-C6 (BPL-C6 = bis-1,10-phenanthroline-carbon-6), prepared using click chemistry that demonstrates site-specific DNA recognition with low micromolar cleavage activity. The BPL-C6 ligand was designed to force two redox-active copper centres-central for enhancing AMN activity-to bind DNA, via two phenanthroline ligands separated by an aliphatic linker.

Inter-Session Reliability of Functional Performance and Muscle Power in Adults With Severe Obesity.

Reliable and sensitive testing of physical function is crucial for assessing the effects of treatment or exercise intervention in various patient populations. The present study investigated the test-retest reliability and sensitivity (smallest detectable difference: SDD) of selected physical performance tests commonly used in clinical rehabilitation, including tests of habitual and maximal walking speed, walking endurance capacity, handgrip strength (HGS), and lower limb muscle power (Sit-to-Stand (STS), stair climb) in adults with severe obesity meeting the criteria for bariatric surgery. Thirty-two adults (BMI 43.

The factor structure of the International Trauma Questionnaire - Heywood cases in confirmatory factor analysis.

A number of studies have tested the factor structure of the suggested ICD-11 symptom criteria for PTSD and complex PTSD (CPTSD) across various trauma populations, finding support for two different models in line with the ICD-11 theoretical rationale. Here, we aim to explore the factor structure of the Danish version of the International Trauma Questionnaire (ITQ) by testing two alternative factor models that have previously gained support in a large sample of treatment-seeking veterans. Treatment-seeking Danish soldiers and veterans ( = 599) recruited from the Military Psychology Department in the Danish Defence completed the International Trauma Questionnaire (ITQ).