Publications by authors named "O Orwar"

Article Synopsis
  • KRAS is a small GTPase that acts as a switch for cell signaling, and mutations in KRAS are linked to various cancers, notably pancreatic, lung, and colorectal cancers.
  • Recent efforts to target specific KRAS mutations, particularly G12C and G12D, have shown some success, but other mutations like G12V and G13D remain difficult to treat.
  • The study presents a new KRAS G13D conformer structure that could be targeted by a developed monoclonal antibody, which effectively inhibited KRAS signaling in cancer cells, suggesting a new avenue for therapeutic development against this mutation.
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Several important drug targets, e.g., ion channels and G protein-coupled receptors, are extremely difficult to approach with current antibody technologies.

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Significant strides have been made in the development of in vitro systems for disease modelling. However, the requirement of microenvironment control has placed limitations on the generation of relevant models. Herein, we present a biological tissue printing approach that employs open-volume microfluidics to position individual cells in complex 2D and 3D patterns, as well as in single cell arrays.

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Cancer cells adapt to their inherently increased oxidative stress through activation of the glutathione (GSH) and thioredoxin (TXN) systems. Inhibition of both of these systems effectively kills cancer cells, but such broad inhibition of antioxidant activity also kills normal cells, which is highly unwanted in a clinical setting. We therefore evaluated targeting of the TXN pathway alone and, more specifically, selective inhibition of the cytosolic selenocysteine-containing enzyme TXN reductase 1 (TXNRD1).

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Background: Among the various fluidic control technologies, microfluidic devices are becoming powerful tools for pharmacological studies using brain slices, since these devices overcome traditional limitations of conventional submerged slice chambers, leading to better spatiotemporal control over delivery of drugs to specific regions in the slices. However, microfluidic devices are not yet fully optimized for such studies.

New Method: We have recently developed a multifunctional pipette (MFP), a free standing hydrodynamically confined microfluidic device, which provides improved spatiotemporal control over drug delivery to biological tissues.

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