Small-Molecule Activation of Protein Phosphatase 2A Counters Bleomycin-Induced Fibrosis in Mice.

The activity of protein phosphatase 2A (PP2A), a serine-threonine phosphatase, is reduced in the lung fibroblasts of idiopathic pulmonary fibrosis (IPF) patients. The objective of this study was to determine whether the reactivation of PP2A could reduce fibrosis and preserve the pulmonary function in a bleomycin (BLM) mouse model. Here, we present a new class of direct small-molecule PP2A activators, diarylmethyl-pyran-sulfonamide, exemplified by ATUX-1215.

Evaluating Novel Protein Phosphatase 2A Activators as Therapeutics for Emphysema.

The activity of PP2A (protein phosphatase 2A), a serine-threonine phosphatase, is reduced by chronic cigarette smoke (SM) exposure and α-1 antitrypsin (AAT) deficiency, and chemical activation of PP2A reduces the loss of lung function in SM-exposed mice. However, the previously studied PP2A-activator tricyclic sulfonamide compound DBK-1154 has low stability to oxidative metabolism, resulting in fast clearance and low systemic exposure. Here we compare the utility of a new more stable PP2A activator, ATUX-792, versus DBK-1154 for the treatment of SM-induced emphysema.

Ability of the Khorana score to predict recurrent thromboembolism in cancer patients with ischemic stroke.

Cancer patients with acute ischemic stroke (AIS) are high-risk for recurrent thromboembolic events (RTE). Currently, no risk stratification model exists to predict RTE in this population. We tested the hypothesis that the Khorana score, a validated risk model for predicting venous thromboembolism in cancer patients, can effectively classify RTE risk in cancer patients with AIS.

Enoxaparin vs Aspirin in Patients With Cancer and Ischemic Stroke: The TEACH Pilot Randomized Clinical Trial.

This randomized clinical trial compares anticoagulation vs antiplatelet therapy in patients with cancer and acute ischemic stroke.

Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial.

Purpose: High-grade gliomas are associated with a dismal prognosis. Notch inhibition via the gamma-secretase inhibitor RO4929097 has emerged as a potential therapeutic option based on modulation of the cancer-initiating cell (CIS) population and a presumed antiangiogenic role.

Experimental Design: In this phase 0/I trial, 21 patients with newly diagnosed glioblastoma or anaplastic astrocytoma received RO4929097 combined with temozolomide and radiotherapy.

Obsessive-compulsive-like behaviors in house mice are attenuated by a probiotic (Lactobacillus rhamnosus GG).

Two experiments examined probiotic pretreatment (Lactobacillus rhamnosus GG) on obsessive-compulsive disorder (OCD)-like behavior induction by RU 24969 in BALB/cJ house mice. In the first experiment, two groups were defined by their daily pretreatment by oral gavage of either (a) L. rhamnosus (1×10⁹ CFU/day) or (b) the saline vehicle.