Search

To identify cancer-associated gene regulatory changes, we generated single-cell chromatin accessibility landscapes across eight tumor types as part of The Cancer Genome Atlas. Tumor chromatin accessibility is strongly influenced by copy number alterations that can be used to identify subclones, yet underlying cis-regulatory landscapes retain cancer type-specific features. Using organ-matched healthy tissues, we identified the "nearest healthy" cell types in diverse cancers, demonstrating that the chromatin signature of basal-like-subtype breast cancer is most similar to secretory-type luminal epithelial cells. Neural network models trained to learn regulatory programs in cancer revealed enrichment of model-prioritized somatic noncoding mutations near cancer-associated genes, suggesting that dispersed, nonrecurrent, noncoding mutations in cancer are functional. Overall, these data and interpretable gene regulatory models for cancer and healthy tissue provide a framework for understanding cancer-specific gene regulation.

Increased drug resistance has reduced efficiency of chemotherapic drugs such as Doxorubicin (Dox). Scrophularia amplexicaulis (Scr) is one of the most important medicinal plants in Iran that has anti-cancer activity. The aim of this study was to investigate a novel approach to enhance therapeutic efficacy of Dox (as a chemotherapeutic agent) by co-administration of Scr (as a bioactive herbal compound) in gastric cancer treatment. In the present study, effects of Dox, Scr, and their combinations (Scr-Dox) were evaluated on viability and proliferation of two gastric cancer cell lines (AGS and MKN28). Moreover, morphological changes, invasion, migration, colony formation, and apoptosis rate in the treated cancer cells were evaluated. Expression of BAX, BCL2, SAMC, SURVIVIN, CASP9, P53, MMP9, and MMP2 in the treated cancer cells and untreated controls were evaluated by Real-Time PCR method. Treatments of cancer cells by Scr, Dox, and Scr-Dox significantly decreased proliferation, invasion, migration, and colony formation of gastric cancer cells. Treatments of cancer cells by Scr, Dox, and Scr-Dox significantly increased apoptosis rate as well as decreased cells mobility through modification of apoptosis- and metastasis-related genes expression. However, anti-cancer activity of Scr-Dox combination was significantly more than Scr and Dox treatments alone. In general, we demonstrated that Scr-Dox combination therapy exerts more profound anti-cancer effects on AGS and MKN28 cell lines than Scr and Dox monotherapy., (© 2023 Wiley Periodicals LLC.)

Objectives: Dementia is a growing health concern. Persons with dementia experience higher levels of anxiety and depression, which correlates with poorer quality of life, disability and hospitalization. This is one of the few studies to use a longitudinal design to assess the impact of expressed emotion (EE) on well-being in dementia over time., Methods: Sixty-one people with dementia and their main informal caregiver were recruited from memory services. Caregiver EE was coded from a Camberwell Family Interview conducted at time one. Person with dementia's outcome measures (quality of life, depression and anxiety) were collected at time one and at 6-months follow-up., Results: Caregiver high EE was associated with higher levels of depression in people with dementia and greater anxiety at follow-up. Emotional over involvement predicted greater anxiety and critical comments predicted greater depression. Low EE appeared to have a protective effect on well-being in people with dementia. People with dementia with low EE caregivers experienced a small reduction in depression and anxiety over time, whereas those with high-EE caregivers maintained baseline levels of depression and anxiety., Conclusions: Caregiver high EE is associated with poorer psychological outcomes for people with dementia over time. Psychological therapies, such as cognitive behavioural therapy informed family interventions should be used to reduce high EE within carer and person with dementia relationships., (© 2023 The Authors. British Journal of Clinical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)