Purpose: Oral oncolytics have improved survival in hematological cancers like chronic myeloid leukemia, chronic lymphocytic leukemia/small lymphocytic lymphoma, and multiple myeloma; however, it is unclear of the extent to which initiating these treatments might impact adherence to oral therapies for pre-existing comorbid chronic conditions.
Methods: Adults diagnosed with and prescribed oral oncolytics for chronic myeloid leukemia, chronic lymphocytic leukemia/small lymphocytic lymphoma, or multiple myeloma between 2013 and 2016 and with continuous eligibility six months before and after oral oncolytic initiation were identified from the Truven Health MarketScan databases. Among those identified, patients with pre-existing diabetes, hypertension, and/or hyperlipidemia with ≥1 fill for oral comorbid therapies were selected.
Intermittent cyclic stretching and incrementally increasing strain amplitude cyclic stretching were explored to overcome the reported adaptation of fibroblasts in response to constant amplitude cyclic stretching, with the goals of accelerating collagen production and understanding the underlying cell signaling. The effects of constant amplitude, intermittent, and incremental cyclic stretching regimens were investigated for dermal fibroblasts entrapped in a fibrin gel by monitoring the extracellular signal-regulated kinase (ERK1/2) and p38 pathways, collagen transcription, and finally the deposited collagen protein. Activation of ERK1/2, which has been shown to be necessary for stretch-induced collagen transcription, was maximal at 15 min and decayed by 1 h.
View Article and Find Full Text PDFDiseased aortic valves often require replacement, with over 30% of the current aortic valve surgeries performed in patients who will outlive a bioprosthetic valve. While many promising tissue-engineered valves have been created in the lab using the cell-seeded polymeric scaffold paradigm, none have been successfully tested long-term in the aortic position of a pre-clinical model. The high pressure gradients and dynamic flow across the aortic valve leaflets require engineering a tissue that has the strength and compliance to withstand high mechanical demand without compromising normal hemodynamics.
View Article and Find Full Text PDFA cyclic stretch and perfusion bioreactor was designed to culture large diameter engineered tissue tubes for heart valve applications. In this bioreactor, tubular tissues consisting of dermal fibroblasts in a sacrificial fibrin gel scaffold were placed over porated latex support sleeves and mounted in a custom bioreactor. Pulsatile flow of culture medium into the system resulted in cyclic stretching as well as ablumenal, lumenal, and transmural flow (perfusion).
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