The clinical effect of the dual-targeting strategy involving PI3K/AKT/mTOR and RAS/MEK/ERK pathways in patients with advanced cancer.

Purpose: This study evaluated the clinical relevance of the dual-targeting strategy involving PI3K/AKT/mTOR and RAF/MEK/ERK pathways.

Experimental Design: We investigated safety, efficacy, and correlations between tumor genetic alterations and clinical benefit in 236 patients with advanced cancers treated with phase I study drugs targeting phosphoinositide 3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) pathways in our Phase I Clinical Trials Program.

Results: Seventy-six (32.

Effects of chronic dietary and waterborne cadmium exposures on the contamination level and reproduction of Daphnia magna.

Regulatory assessments of metal toxicity on freshwater organisms assume that toxic effects are caused by dissolved metals. In aquatic systems, organisms are exposed to both dissolved and particulate-bound metals. In this study, the chronic toxicity of dietary cadmium (Cd) on the reproduction and Cd body burden of Daphnia magna was investigated.