The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis.

The contribution of epigenetic dysregulation to metastasis remains understudied. Through a meta-analysis of gene expression datasets followed by a mini-screen, we identified Plant Homeodomain Finger protein 8 (PHF8), a histone demethylase of the Jumonji C protein family, as a previously unidentified prometastatic gene in melanoma. Loss- and gain-of-function approaches demonstrate that PHF8 promotes cell invasion without affecting proliferation in vitro and increases dissemination but not subcutaneous tumor growth in vivo, thus supporting its specific contribution to the acquisition of metastatic potential.

Baseline antibody profiles predict toxicity in melanoma patients treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (anti-CTLA-4, anti-PD-1, or the combination) enhance anti-tumor immune responses, yielding durable clinical benefit in several cancer types, including melanoma. However, a subset of patients experience immune-related adverse events (irAEs), which can be severe and result in treatment termination. To date, no biomarker exists that can predict development of irAEs.

Collateralization of projections from the rostral ventrolateral medulla to the rostral and caudal thoracic spinal cord in felines.

Stimulation of vestibular receptors elicits distinct changes in blood flow to the forelimb and hindlimb, showing that the nervous system has the capacity to produce changes in sympathetic outflow which are specific for a particular region of the body. However, it is unclear whether the rostral ventrolateral medulla (RVLM), the primary region of the brainstem that regulates sympathetic outflow to vascular smooth muscle, has the appropriate connectivity with sympathetic preganglionic neurons to generate anatomically patterned responses. To make this determination, the retrograde fluorescent tracer Fast Blue was injected into the T(4) spinal cord segment of cats, which regulates upper body blood flow, whereas Fluoro-Ruby was injected into the T(10) segment to label projections to a region of the spinal cord that regulates lower body blood flow.

The relationship between basal cisterns on CT and time-linked intracranial pressure in paediatric head injury.

Purpose: Although intracranial pressure (ICP) monitoring is a cornerstone of care for severe traumatic brain injury (TBI), the indications for ICP monitoring in children are unclear. Often, decisions are based on head computed tomography (CT) scan characteristics. Arguably, the patency of the basal cisterns is the most commonly used of these signs.