Oral squamous cell carcinoma (OSCC) is an epithelial malignancy of the oral cavity, which is the most common of the human head and neck cancers, excluding skin and thyroid cancers (Villa et al., 2011).It is estimated that 50% of people diagnosed with OSCC succumb every year-mainly due to late detection when the cancer has already spread (Warnakulasuriya, 2009). Tobacco smoking and alcohol consumption continue to be two of the most common risk factors of OSCC (Blot et al., 1988;Kumar et al., 2016). The 5-year survival rates for OSCC vary significantly based on the stage of cancer at diagnosis. According to the National Cancer Institute, the 5-year survival rate is about 82% for Stage I OSCC. This rate will drop almost fivefold in Stage IV OSCC in which the 5-year survival rate is only 18%
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 (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 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.
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