Publications by authors named "K J Steadman"

Background: Xerostomia is a common and difficult symptom experienced by patients with cancer. Pilocarpine is a cholinergic agent that stimulates salivation.

Aim: To assess the feasibility of conducting a N-of-1 trial to determine the efficacy of pilocarpine orally dissolving tablets in patients with xerostomia.

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Background: The Australian National Perinatal Data Collection collates all live and stillbirths from States and Territories in Australia. In that database, maternal cigarette smoking is noted twice (smoking <20 weeks gestation; smoking >20 weeks gestation). Cannabis use and other forms of nicotine use, for example vaping and nicotine replacement therapy, are nor reported.

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Article Synopsis
  • Targeted protein degradation (TPD) using the ubiquitin proteasome system (UPS) is emerging as a promising approach for drug discovery, focusing on eliminating harmful proteins.
  • The study identifies and optimizes a small molecule, PLX-3618, which selectively degrades the BRD4 protein, demonstrating strong antitumor effects in lab tests and animal models.
  • The research uncovers DCAF11 as the crucial E3 ligase that activates this degradation process, establishing a specific interaction among BRD4, PLX-3618, and DCAF11.
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Targeted protein degradation (TPD) using the ubiquitin proteasome system (UPS) is a rapidly growing drug discovery modality to eliminate pathogenic proteins. Strategies for TPD have focused on heterobifunctional degraders that often suffer from poor drug-like properties, and molecular glues that rely on serendipitous discovery. Monovalent "direct" degraders represent an alternative approach, in which small molecules bind to a target protein and induce degradation of that protein through the recruitment of an E3 ligase complex.

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Background: Direct comparison of tumor microenvironment of matched lung cancer biopsies and pleural effusions (PE) from the same patients is critical in understanding tumor biology but has not been performed. This is the first study to compare the lung cancer and PE microenvironment by single-cell RNA sequencing (scRNA-seq).

Methods: Matched lung cancer biopsies and PE were obtained prospectively from ten patients.

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