enhances tumorigenic potential of lung cells by exhibiting synergy with mutation and altering response to environmental stress.

Although is a recurrent splicing factor mutation in lung adenocarcinoma (ADC), alone is insufficient for producing tumors in previous models. Because lung ADCs with frequently have co-occurring mutations and smoking histories, we hypothesized that tumor-forming potential arises from interacting with oncogenic and environmental stress. To elucidate the effect of co-occurring with a second mutation, we generated human bronchial epithelial cells (HBEC3kt) with co-occurring and .

Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors.

Purpose: MEK inhibitors (MEKi) lack monotherapy efficacy in most RAS-mutant cancers. BCL-xL is an anti-apoptotic protein identified by a synthetic lethal shRNA screen as a key suppressor of apoptotic response to MEKi.

Patients And Methods: We conducted a dose escalation study (NCT02079740) of the BCL-xL inhibitor navitoclax and MEKi trametinib in patients with RAS-mutant tumors with expansion cohorts for: pancreatic, gynecologic (GYN), non-small cell lung cancer (NSCLC), and other cancers harboring KRAS/NRAS mutations.

Combined PD-1, BRAF and MEK inhibition in BRAF colorectal cancer: a phase 2 trial.

While BRAF inhibitor combinations with EGFR and/or MEK inhibitors have improved clinical efficacy in BRAF colorectal cancer (CRC), response rates remain low and lack durability. Preclinical data suggest that BRAF/MAPK pathway inhibition may augment the tumor immune response. We performed a proof-of-concept single-arm phase 2 clinical trial of combined PD-1, BRAF and MEK inhibition with sparatlizumab (PDR001), dabrafenib and trametinib in 37 patients with BRAF CRC.

Stability of Attention Performance of Adults with ADHD over Time: Evidence from Repeated Neuropsychological Assessments in One-Month Intervals.

Neuropsychological assessments of attention are valuable sources of information in the clinical evaluation of adults with attention-deficit/hyperactivity disorder (ADHD). However, it is unclear whether the attention performance of adults with ADHD is stable or fluctuates over time, which is of great importance in the interpretation of clinical assessments. This study aimed to explore the stability of attention performance of adults with ADHD in repeated assessments at one-month intervals.

Identification of a minority population of LMO2 breast cancer cells that integrate into the vasculature and initiate metastasis.

Metastasis is responsible for most breast cancer-related deaths; however, identifying the cellular determinants of metastasis has remained challenging. Here, we identified a minority population of immature / tumor epithelial cells in human breast tumor biopsies that display angiogenic features and are marked by the expression of the oncogene, . Higher abundance of basal cells correlated with tumor endothelial content and predicted poor distant recurrence-free survival in patients.