We have previously shown that Wnt5A and ROR2, an orphan tyrosine kinase receptor, interact to mediate melanoma cell motility. In other cell types, this can occur through the interaction of ROR2 with the cytoskeletal protein filamin A. Here, we found that filamin A protein levels correlated with Wnt5A levels in melanoma cells. Small interfering RNA (siRNA) knockdown of WNT5A decreased filamin A expression. Knockdown of filamin A also corresponded to a decrease in melanoma cell motility. In metastatic cells, filamin A expression was predominant in the cytoplasm, which western analysis indicated was due to the cleavage of filamin A in these cells. Treatment of nonmetastatic melanoma cells with recombinant Wnt5A increased filamin A cleavage, and this could be prevented by the knockdown of ROR2 expression. Further, BAPTA-AM chelation of intracellular calcium also inhibited filamin A cleavage, leading to the hypothesis that Wnt5A/ROR2 signaling could cleave filamin A through activation of calcium-activated proteases, such as calpains. Indeed, WNT5A knockdown decreased calpain 1 expression, and by inhibiting calpain 1 either pharmacologically or using siRNA, it decreased cell motility. Our results indicate that Wnt5A activates calpain-1, leading to the cleavage of filamin A, which results in a remodeling of the cytoskeleton and an increase in melanoma cell motility.

Methicillin-resistant Staphylococcus aureus (MRSA) has become an increasingly common cause of diffi cult-to-treat head and neck infections. We report a retrospective analysis of 3 cases of MRSA otorrhea treated in our clinic between 2007 and 2009. Culture analysis of otorrhea isolates revealed MRSA infections with identical drug sensitivities. Treatment success was achieved using combinations of linezolid with gentamicin ear drops for 3 to 4 weeks or trimethoprim/sulfamethoxazole (TMP/SMX) with gentamicin drops for 6 weeks. Th is study illustrates the importance of determining individual drug sensitivities for optimal treatment and maintaining current knowledge of the local MRSA strains. Empiric combination therapy of TMP/SMX with gentamicin is an eff ective fi rst-line treatment for MRSA otorrhea. Regional diff erences in clindamycin sensitivities warrant clinical discretion. Fluoroquinolones should be avoided because of high rates of resistance unless culture sensitivity determines that they are appropriate. First-line agents for severe infections include combination therapy with vancomycin or linezolid. Multiple Sinuses / One Solution The XprESS™ Multi-Sinus Dilation Tool is as easy to use as a sinus seeker. For use in treating frontal, sphenoid and maxillary sinuses, XprESS provides ENTs with a single tool for treating multiple sinuses during FESS. The tool consists of a curved sinus seeker outfitted with a slideable dilation balloon and malleable tip that can be reshaped. Locate, inflate and dilate. Any questions Indications for use: To access and treat the frontal recesses, sphenoid sinus ostia and maxillary ostia/ethmoid infundibula in adults using a trans-nasal approach. The bony sinus outflow tracts are remodeled by balloon displacement of adjacent bone and paranasal sinus structures. Please see the Instructions For Use for a complete listing on contraindications, warnings, precautions, and adverse events.

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