Rare but Recurrent ROS1 Fusions Resulting From Chromosome 6q22 Microdeletions are Targetable Oncogenes in Glioma.

Purpose: Gliomas, a genetically heterogeneous group of primary central nervous system tumors, continue to pose a significant clinical challenge. Discovery of chromosomal rearrangements involving kinase genes has enabled precision therapy, and improved outcomes in several malignancies.

Experimental Design: Positing that similar benefit could be accomplished for patients with brain cancer, we evaluated The Cancer Genome Atlas (TCGA) glioblastoma dataset.

Prioritization schema for immunotherapy clinical trials in glioblastoma.

Background: Emerging immunotherapeutic strategies for the treatment of glioblastoma (GBM) such as dendritic cell (DC) vaccines, heat shock proteins, peptide vaccines, and adoptive T-cell therapeutics, to name a few, have transitioned from the bench to clinical trials. With upcoming strategies and developing therapeutics, it is challenging to critically evaluate the practical, clinical potential of individual approaches and to advise patients on the most promising clinical trials.

Methods: The authors propose a system to prioritize such therapies in an organized and data-driven fashion.

Genome-scale CRISPR-Cas9 knockout screening in human cells.

The simplicity of programming the CRISPR (clustered regularly interspaced short palindromic repeats)-associated nuclease Cas9 to modify specific genomic loci suggests a new way to interrogate gene function on a genome-wide scale. We show that lentiviral delivery of a genome-scale CRISPR-Cas9 knockout (GeCKO) library targeting 18,080 genes with 64,751 unique guide sequences enables both negative and positive selection screening in human cells. First, we used the GeCKO library to identify genes essential for cell viability in cancer and pluripotent stem cells.

Mechanism of transcorneal permeation of pilocarpine.

The mechanism of transcorneal permeation of pilocarpine has been investigated in relation to the physicochemical properties of the permeating species and its interaction with the membrane biophase. In vitro corneal transport experiments suggested the transport of un-ionized as well as ionized pilocarpine species across the corneal membrane. However, the permeability of the ionized pilocarpine species was 4.