MEK1/2 inhibition transiently alters the tumor immune microenvironment to enhance immunotherapy efficacy against head and neck cancer.

Background: Although the mitogen-activated protein kinases (MAPK) pathway is hyperactive in head and neck cancer (HNC), inhibition of MEK1/2 in HNC patients has not shown clinically meaningful activity. Therefore, we aimed to characterize the effect of MEK1/2 inhibition on the tumor microenvironment (TME) of MAPK-driven HNC, elucidate tumor-host interaction mechanisms facilitating immune escape on treatment, and apply rationale-based therapy combination immunotherapy and MEK1/2 inhibitor to induce tumor clearance.

Methods: Mouse syngeneic tumors and xenografts experiments were used to analyze tumor growth in vivo.

A Comparison of Falls and Dizziness Handicap by Vestibular Diagnosis.

Purpose: There is a paucity of data that directly compares the falls rate and dizziness handicap of different vestibular diagnoses. The purpose of this study is to compare the falls rate and dizziness handicap of common vestibular diagnoses encountered among a cohort of vestibular patients at a single institution.

Method: We conducted a retrospective cross-sectional study of patients evaluated for dizziness at a tertiary care center vestibular clinic between August 1, 2017, and March 19, 2019.

[Spigelian hernia and cholecystolithiasis treated laparoscopically].

The authors present the laparoscopic treatment of the uncommon Spigelian hernia together with gallstones at a 50-years old woman.

Structural requirements for neural cell adhesion molecule-heparin interaction.

Two biological domains have been identified in the amino terminal region of the neural cell adhesion molecule (NCAM): a homophilic-binding domain, responsible for NCAM-NCAM interactions, and a heparin-binding domain (HBD). It is not known whether these two domains exist as distinct structural entities in the NCAM molecule. To approach this question, we have further defined the relationship between NCAM-heparin binding and cell adhesion.

Nerve fibers surrounding intracranial and extracranial vessels from human and other species contain dynorphin-like immunoreactivity.

Dynorphin B(20-32) was visualized by immunohistochemistry in guinea-pig and rat perivascular nerve fibers and was measured by radioimmunoassay within the walls of feline, canine, bovine and human cephalic and systemic arteries and veins. Canine vessels contained the highest levels. When human blood vessels or trigeminal ganglia were subjected to reverse-phase high-performance liquid chromatography, dynorphin immunoreactivity exhibited a retention time identical to that of synthetic dynorphin B.

Dynorphin B-containing perivascular axons and sensory neurotransmitter mechanisms in brain blood vessels.

This is the first report demonstrating the existence of opiate-containing nerve fibers surrounding brain blood vessels. Dynorphin B, a tridecapeptide and potent opiate analgesic, was visualized by immunohistochemistry in guinea pig cerebral arteries comprising the circle of Willis and was measured by radioimmunoassay in canine middle cerebral arteries. This peptide, reportedly present in dorsal root ganglion cells, was observed by others to decrease the depolarization-induced release of substance P from primary sensory axons and, by so doing, to retard the development of neurogenic inflammation in target tissues.

Tracheal submucosal gland serous cells stimulated in vitro with adrenergic and cholinergic agonists. A morphometric study.

A morphometric analysis was made of alterations in serous cell structure induced by adrenergic and cholinergic agonists. Ferret tracheal rings were exposed for 30 min in vitro to one of the following agonists: phenylephrine, terbutaline, or methacholine (all at 10(-5) M). Controls were incubated similarly in medium containing no drugs or medium containing both the agonist and an excess of the appropriate antagonist (phentolamine, propranolol or atropine, all at 10(-4) M).