Dual inhibition of thioredoxin reductase and proteasome is required for auranofin-induced paraptosis in breast cancer cells.

Auranofin (AF), a gold (I)-containing phosphine compound, is being investigated for oncological application as a repurposed drug. We show here that 4~5 µM AF induces paraptosis, a non-apoptotic cell death mode characterized by dilation of the endoplasmic reticulum (ER) and mitochondria, in breast cancer cells. Although the covalent inhibition of thioredoxin reductase (TrxR), an enzyme that critically controls intracellular redox homeostasis, is considered the primary mechanism of AF's anticancer activity, knockdown of TrxR1 did not induce paraptosis.

ISRIB plus bortezomib triggers paraptosis in breast cancer cells via enhanced translation and subsequent proteotoxic stress.

Despite the success of proteasome inhibitors (PIs) in treating hematopoietic malignancies, including multiple myeloma (MM), their clinical efficacy is limited in solid tumors. In this study, we investigated the involvement of the integrated stress response (ISR), a central cellular adaptive program that responds to proteostatic defects by tuning protein synthesis rates, in determining the fates of cells treated with PI, bortezomib (Bz). We found that Bz induces ISR, and this can be reversed by ISRIB, a small molecule that restores eIF2B-mediated translation during ISR, in both Bz-sensitive MM cells and Bz-insensitive breast cancer cells.

The Frequency of Axial Deposition in Korean Patients With Gout at a Tertiary Spine Center.

This study aimed to describe the frequency of axial deposition (axial gout) and determine the associated factors in patients with gout who presented to a spine clinic in Korea. We enrolled 95 Korean patients who visited our spine center from March 2012 to February 2016 and who had been previously diagnosed with gout and had available computed tomography (CT) images of the vertebral columns. Axial gout was defined as the presence of erosions or tophi in the vertebral endplate or facet joint.

Comparison of Clinical Outcomes between Idiopathic Frozen Shoulder and Diabetic Frozen Shoulder After a Single Ultrasound-Guided Intra-Articular Corticosteroid Injection.

There is no consensus on the use of intra-articular corticosteroid injections in diabetic frozen shoulder (FS). Thus, we aimed to compare clinical outcomes after intra-articular corticosteroid injections in patients with diabetic FS and idiopathic FS. Data collected from 142 FS patients who received glenohumeral joint intra-articular corticosteroid injections were retrospectively reviewed.