A phase 1b study evaluating the safety and preliminary efficacy of berzosertib in combination with gemcitabine in patients with advanced non-small cell lung cancer.

Objectives: Berzosertib (formerly M6620, VX-970) is an intravenous, highly potent and selective, first-in-class ataxia telangiectasia and Rad3-related (ATR) protein kinase inhibitor. We assessed the safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of berzosertib plus gemcitabine in an expansion cohort of patients with advanced non-small cell lung cancer (NSCLC). The association of efficacy with TP53 status and other tumor markers was also explored.

CEP41-mediated ciliary tubulin glutamylation drives angiogenesis through AURKA-dependent deciliation.

The endothelial cilium is a microtubule-based organelle responsible for blood flow-induced mechanosensation and signal transduction during angiogenesis. The precise function and mechanisms by which ciliary mechanosensation occurs, however, are poorly understood. Although posttranslational modifications (PTMs) of cytoplasmic tubulin are known to be important in angiogenesis, the specific roles of ciliary tubulin PTMs play remain unclear.

Quantitative Proteomic Analysis of Changes Related to Age and Calorie Restriction in Rat Liver Tissue.

Calorie restriction (CR) is the most frequently studied mechanism for increasing longevity, protecting against stress, and delaying age-associated diseases. Most studies have initiated CR in young animals to determine the protective effects against aging. Although aging phenomena are well-documented, the molecular mechanisms of aging and CR remain unclear.

Comparison of bacterial communities in leachate from decomposing bovine carcasses.

Objective: Burial is associated with environmental effects such as the contamination of ground or surface water with biological materials generated during the decomposition process. Therefore, bacterial communities in leachates originating from the decomposing bovine carcasses were investigated.

Methods: To understand the process of bovine (Hanwoo) carcass decomposition, we simulated burial using a lab-scale reactor with a volume of 5.

Patient fibroblasts-derived induced neurons demonstrate autonomous neuronal defects in adult-onset Krabbe disease.

Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by defective β-galactosylceramidase (GALC), a lysosomal enzyme responsible for cleavage of several key substrates including psychosine. Accumulation of psychosine to the cytotoxic levels in KD patients is thought to cause dysfunctions in myelinating glial cells based on a comprehensive study of demyelination in KD. However, recent evidence suggests myelin-independent neuronal death in the murine model of KD, thus indicating defective GALC in neurons as an autonomous mechanism for neuronal cell death in KD.

ADSSL1 mutation relevant to autosomal recessive adolescent onset distal myopathy.

Objective: Distal myopathy is a heterogeneous group of muscle diseases characterized by predominant distal muscle weakness. A study was done to identify the underlying cause of autosomal recessive adolescent onset distal myopathy.

Methods: Four patients from 2 unrelated Korean families were evaluated.

Phase I study of two schedules of oral S-1 in combination with fixed doses of oxaliplatin and bevacizumab in patients with advanced solid tumors.

Background: S-1 is a novel oral agent combining the 5-fluorouracil (FU) prodrug tegafur with gimeracil and oteracil, which inhibit 5-FU degradation by dihydropyrimidine dehydrogenase and phosphorylation within the gastrointestinal tract, respectively. The study was designed to identify the maximum tolerable dose and the dose-limiting toxicities of two schedules of S-1 combined with oxaliplatin and bevacizumab, in advanced solid tumor patients.

Methods: Schedule A: S-1 was administered orally at 20 mg/m(2) twice daily for 14 consecutive days, escalated by 5 mg/m(2), with fixed-dose intravenous bevacizumab 7.