Covalent Inhibitors of KEAP1 with Exquisite Selectivity.

The NRF2-KEAP1 interaction is central for cytoprotection against stresses, giving it high clinical significance. Covalent modification of KEAP1 is an efficient approach, but the covalent inhibitors used in the clinic carry undesired side effects originating in their moderate selectivity. Starting with a phenotypic screen, we identified a new covalent inhibitor chemotype that was optimized to deliver a series of potent and highly selective KEAP1 binders.

Differential immunomodulatory effects of epirubicin/cyclophosphamide and docetaxel in breast cancer patients.

Background: Epirubicin/cyclophosphamide (EC) and docetaxel (D) are commonly used in a sequential regimen in the neoadjuvant treatment of early, high-risk or locally advanced breast cancer (BC). Novel approaches to increase the response rate combine this treatment with immunotherapies such as PD-1 inhibition. However, the expected stimulatory effect on lymphocytes may depend on the chemotherapy backbone.

Structural Connectivity Reorganization Based on DTI after Cingulotomy in Obsessive-Compulsive Disorder.

Bilateral cingulotomy is a procedure applied to patients with obsessive-compulsive disorder (OCD). This report presents the structural changes occurring within the forceps minor and arcuate fascicles nerve fibers after a successful bilateral anterior cingulotomy in the patient with refractory OCD. Cingulotomy mainly affects the values of FA, MD, and ADC in the treatment of the examined nerve bundles.

Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer.

Purpose: Estrogen receptor (ER) expression is a prognostic parameter in breast cancer, and a prerequisite for the use of endocrine therapy. In ER+ early breast cancer, however, no receptor-associated biomarker exists that identifies patients with a particularly favorable outcome. We have investigated the value of ESR1 amplification in predicting the long-term clinical outcome in tamoxifen-treated postmenopausal women with endocrine-responsive breast cancer.