Publications by authors named "Dylan Maxwell"
Introduction: Amphibious warships are now being deployed with established 3D printing departments capable of designing and manufacturing parts for aircraft or ship engineering needs. The ability to print with a variety of materials from heat stable polymers to metal constructs can be useful to shipboard medical departments to replenish consumable and durable supplies. This report aims to demonstrate the potential benefit of leveraging the afloat additive manufacturing capabilities for medical parts and supplies while deployed at sea.
View Article and Find Full Text PDFBackground: The U.S. military utilizes small, forward deployed surgical teams to provide Role 2 surgical care in austere environments.
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- Resistance to chemotherapy in acute lymphoblastic leukemia (ALL) is a significant reason for treatment failure, with challenges in current testing methods for drug sensitivity.
- A new fluorescence imaging method allows for efficient profiling of drug sensitivity in primary ALL cells using co-culture with stromal cells and a panel of 40 drugs, aiming to identify individual resistance patterns.
- This automated approach enhances testing efficiency by needing fewer cells and reduces the labor and time required, integrating drug sensitivity data with genomic profiling for a more precise treatment strategy.
Contemporary chemotherapy for childhood acute lymphoblastic leukemia (ALL) is risk-adapted based on clinical features, leukemia genomics and minimal residual disease (MRD); however, the pharmacological basis of these prognostic variables remains unclear. Analyzing samples from 805 children with newly diagnosed ALL from three consecutive clinical trials, we determined the ex vivo sensitivity of primary leukemia cells to 18 therapeutic agents across 23 molecular subtypes defined by leukemia genomics. There was wide variability in drug response, with favorable ALL subtypes exhibiting the greatest sensitivity to L-asparaginase and glucocorticoids.
View Article and Find Full Text PDFDevelopment of Potent and Selective Janus Kinase 2/3 Directing PG-PROTACs.
ACS Med Chem Lett
March 2022
Aberrant activation of the JAK-STAT signaling pathway has been implicated in the pathogenesis of a range of hematological malignancies and autoimmune disorders. Here we describe the design, synthesis, and characterization of JAK2/3 PROTACs utilizing a phenyl glutarimide (PG) ligand as the cereblon (CRBN) recruiter. SJ10542 displayed high selectivity over GSPT1 and other members of the JAK family and potency in patient-derived ALL cells containing both JAK2 fusions and CRLF2 rearrangements.
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- T-cell acute lymphoblastic leukemia (T-ALL) is a serious blood cancer that shows varying drug responses, with about 44% of children and 17% of adults responding well to the drug dasatinib.
- Research found that the activation of a specific signaling pathway (preTCR-LCK) is key to why some T-ALL cases are sensitive to dasatinib, while other cases are resistant to a different drug called venetoclax.
- The study highlights that the developmental stage of T-cells in leukemia influences which signaling pathways are active, suggesting potential for developing targeted therapies based on a patient's specific leukemia characteristics.
CRLF2-rearranged (CRLF2r) acute lymphoblastic leukemia (ALL) accounts for more than half of Philadelphia chromosome-like (Ph-like) ALL and is associated with a poor outcome in children and adults. Overexpression of CRLF2 results in activation of Janus kinase (JAK)-STAT and parallel signaling pathways in experimental models, but existing small molecule inhibitors of JAKs show variable and limited efficacy. Here, we evaluated the efficacy of proteolysis-targeting chimeras (PROTACs) directed against JAKs.
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