Netrin-1 Stimulates Migration of Neogenin Expressing Aggressive Melanoma Cells.

Netrin-1 is a neural guidance factor that regulates migration and positioning of neural crest-derived cells during embryonic development. Depending on the type of Netrin-1 receptor expression, cells are either attracted or repulsed by Netrin-1. Postnatal expression of Netrin-1 is detected in brain, colon, liver, and kidney, which are common sites of cancer metastasis, including melanoma. Thus, understanding the dynamics between Netrin-1 and its receptors could explain the attraction of melanoma towards these Netrin-1-expressing tissues. Here, we investigate whether the Netrin-1-attractive receptor Neogenin can affect migration of melanoma cells towards a Netrin-1 source. Results from Western blot (WB) analysis show higher expression of Neogenin in aggressive compared to non-aggressive melanoma cells. Cell migration experiments show increased migration of Neogenin-expressing aggressive melanoma cells towards exogenous, soluble recombinant human Netrin-1 and towards a Netrin-1-expressing cell line. Furthermore, WB reveals ERK1/2 activation and increased N-cadherin expression in Neogenin-expressing aggressive melanoma cells treated with rhNetrin-1. Moreover, treatment with anti-Neogenin blocking antibody caused decreased migration towards Netrin-1-expressing cells and reduced ERK1/2 activity in Neogenin-expressing aggressive melanoma cells. These results suggest Neogenin may play a role during migration of melanoma cells towards Netrin-1 via ERK1/2 signaling.

Genicular Artery Embolization for Primary Knee Osteoarthritis.

Genicular artery embolization (GAE) is a novel treatment for knee osteoarthritis (OA) with increasing interest and utilization worldwide. The genicular arteries are selectively embolized using microspheres with subsequent cessation of abnormal synovial hyperemia, a process believed to arrest the inflammatory changes and pain associated with OA. Current data indicate that GAE offers sustained, 6-month improvement in Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and visual analog scale scores in 80 to 85% of patients with mild to moderate OA. As GAE gains traction, future studies are needed to establish its safety and efficacy relative to placebo and other standard-of-care therapies while also characterizing populations for which it is most effective.

Trans-scaphoid lunate dislocation: A case series.

Trans-scaphoid lunate dislocation with volar displacement into the wrist/distal forearm is a devastating injury that most commonly occurs under situations of forceful impact to an extended wrist. Due to ligamentous disruption as well as fragile blood supply, these Mayfield type 4 injuries are associated with significant morbidity and long-term sequelae. Current treatment approaches to lunate dislocations depend on the severity and chronicity of the injury in addition to patient factors, with operative management potentially including ORIF or proximal row carpectomy. We report 5 cases of this rare injury pattern in 4 different patients.

The role of Nodal and Cripto-1 in human oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a common epithelial malignancy of the oral cavity. Nodal and Cripto-1 (CR-1) are important developmental morphogens expressed in several adult cancers and are associated with disease progression. Whether Nodal and CR-1 are simultaneously expressed in the same tumor and how this affects cancer biology are unclear. We investigate the expression and potential role of both Nodal and CR-1 in human OSCC. Immunohistochemistry results show that Nodal and CR-1 are both expressed in the same human OSCC sample and that intensity of Nodal staining is correlated with advanced-stage disease. However, this was not observed with CR-1 staining. Western blot analysis of lysates from two human OSCC line experiments shows expression of CR-1 and Nodal, and their respective signaling molecules, Src and ERK1/2. Treatment of SCC25 and SCC15 cells with both Nodal and CR-1 inhibitors simultaneously resulted in reduced cell viability and reduced levels of P-Src and P-ERK1/2. Further investigation showed that the combination treatment with both Nodal and CR-1 inhibitors was capable of reducing invasiveness of SCC25 cells. Our results show a possible role for Nodal/CR-1 function during progression of human OSCC and that targeting both proteins simultaneously may have therapeutic potential.