FoxO1/Rictor axis induces a nongenetic adaptation to ibrutinib via Akt activation in chronic lymphocytic leukemia.

Bruton tyrosine kinase (BTK) inhibitor therapy induces peripheral blood lymphocytosis in chronic lymphocytic leukemia (CLL), which lasts for several months. It remains unclear whether nongenetic adaptation mechanisms exist, allowing CLL cells' survival during BTK inhibitor-induced lymphocytosis and/or playing a role in therapy resistance. We show that in approximately 70% of CLL cases, ibrutinib treatment in vivo increases Akt activity above pretherapy levels within several weeks, leading to compensatory CLL cell survival and a more prominent lymphocytosis on therapy.

Stromal cells engineered to express T cell factors induce robust CLL cell proliferation in vitro and in PDX co-transplantations allowing the identification of RAF inhibitors as anti-proliferative drugs.

Several in vitro models have been developed to mimic chronic lymphocytic leukemia (CLL) proliferation in immune niches; however, they typically do not induce robust proliferation. We prepared a novel model based on mimicking T-cell signals in vitro and in patient-derived xenografts (PDXs). Six supportive cell lines were prepared by engineering HS5 stromal cells with stable expression of human CD40L, IL4, IL21, and their combinations.

and -A Comparison of Their Decay Patterns on Beech Wood.

Wood-decaying fungi are responsible for the degradation of wood and the alteration in its material properties. (L.) Fr.

Assessing the comparative effectiveness of implementation strategies for professional services to community pharmacy: A systematic review.

Background: Despite the growth of research in how professional services are implemented in the community pharmacy setting, there is limited evidence for which implementation strategy is more effective.

Objective: The aim of this review was to assess the evidence for the comparative effectiveness of implementation strategies for pharmacist delivered professional services in the community pharmacy.

Methods: Studies comparing implementation strategies published in the last 13 years in English were extracted via four databases, combining the topics of 'pharmacy', 'pharmacy services' and 'implementation'.