Overcoming Wnt–β-catenin dependent anticancer therapy resistance in leukaemia stem cells

Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt–β-catenin and PI3K–Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate β-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt–β-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated β-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, β-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated β-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape

Cost-effectiveness of a limited-donorblood program for neonatal red cell transfusions

BACKGROUND: Very-low-birthweight infants have typically been given fresh red cells (RBCs), a practice in which aliquots of RBCs for several infants were issued each day from a single unit. Recently, to limit donor exposures, large volumes of RBCs are reserved for the long-term transfusion support of individual infants. STUDY DESIGN AND METHODS: Medical records were examined retrospectively to assess the costs of a limited-donor program for providing RBC transfusions to very-low-birthweight infants. Costs of multiple- and limited-donor programs were compared by using two samples of 30 consecutive infants treated at The University of Iowa Hospitals and Clinics in 1993 and 1997. Effectiveness was evaluated with respect to the number of donor exposures per infant. RESULTS: The cost, in 1997 dollars, of preparing each small-volume transfusion in the multiple-donor program was $27.86 per transfusion, while that in the limited-donor program was$34.83. This difference was largely attributable to use of white cell reduction in association with the limited-donor program in 1997. Eliminating the costs associated with white cell reduction rendered the costs of the limited- and multiple-donor transfusions comparable. The limited-donor program had donor exposures of 2.0 per infant, while the multiple-donor program had 3.6 exposures per infant (p\u3c0.002). CONCLUSION: The limited-donor blood program reduces donor exposure without adversely affecting costs

Media 1: Reflectance confocal endomicroscope with optical axial scanning for in vivo imaging of the oral mucosa

Originally published in Biomedical Optics Express on 01 November 2014 (boe-5-11-3781

Concurrent and longitudinal dyadic polynomial regression analyses of Big Five traits and relationship satisfaction: Does similarity matter?

Being with a well-matched partner seems essential for a happy relationship. However, past research on personality similarity in couples has reported inconsistent findings. The current study employs a dyadic polynomial regression approach to take into account linear and curvilinear associations between similarity and satisfaction. The concurrent results based on data of 237 couples suggest that beyond actor effects for neuroticism, agreeableness, and conscientiousness and partner effects for agreeableness, similarity plays a negligible role for relationship satisfaction. Longitudinally, two similarity effects emerged. First, if partners reported dissimilar neuroticism levels, male partner reported lower relationship satisfaction. Second, if both partners reported modest levels in openness, female partners reported higher relationship satisfaction. Implications for couples are discussed