BRAF Inhibitors Amplify the Proapoptotic Activity of MEK Inhibitors by Inducing ER Stress in NRAS-Mutant Melanoma.

NRAS mutations in malignant melanoma are associated with aggressive disease requiring rapid antitumor intervention, but there is no approved targeted therapy for this subset of patients. In clinical trials, the MEK inhibitor (MEKi) binimetinib displayed modest antitumor activity, making combinations a requisite. In a previous study, the BRAF inhibitor (BRAFi) vemurafenib was shown to induce endoplasmic reticulum (ER) stress that together with inhibition of the RAF-MEK-ERK (MAPK) pathway amplified its proapoptotic activity in BRAF-mutant melanoma.

PI3K Pathway Inhibition Achieves Potent Antitumor Activity in Melanoma Brain Metastases In Vitro and In Vivo.

Purpose: Great advances have recently been made in treating patients with metastatic melanoma. However, existing therapies are less effective on cerebral than extracerebral metastases. This highlights the potential role of the brain environment on tumor progression and drug resistance and underlines the need for "brain-specific" therapies.

A combined intrauterine and cervical pregnancy diagnosed in the 13th gestational week: which type of management is more feasible and successful?

Objective: To present a case of a simultaneous nonviable cervical pregnancy and viable intrauterine pregnancy diagnosed in the 13th gestational week and to discuss the possible therapeutic options.

Design: Case report.

Setting: University hospital of Münster, Germany.

Mutational analysis of the connexin 36 gene (CX36) and exclusion of the coding sequence as a candidate region for catatonic schizophrenia in a large pedigree.

The murine connexin 36 gene (Cx36) encodes a gap-junction channel protein which is preferentially expressed in brain and retina. The human orthologue CX36 is located on chromosome 15q14, a region recently shown to contain a susceptibility gene for hereditary catatonic schizophrenia. Therefore, CX36 was considered as a positional candidate for mutational analysis.