Asef2 is a recently identified Rho-family guanine nucleotide exchange factor (GEF) that has been implicated in the modulation of actin, but its function in cell migration and adhesion dynamics is not well understood. In this study, we show that Asef2 is an important regulator of cell migration and adhesion assembly and disassembly (turnover). Asef2 localizes with actin at the leading edge of cells. Knockdown of endogenous Asef2 impairs migration and significantly slows the turnover of adhesions. Asef2 enhances both Rac1 and Cdc42 activity in HT1080 cells, but only Rac1 is crucial for the Asef2-promoted increase in migration and adhesion turnover. Phosphoinositide 3-kinase (PI3K) and the serine/threonine kinase Akt are also essential for the Asef2-mediated effects on migration and adhesion turnover. Consistent with this, Asef2 increases the amount of active Akt at the leading edge of cells. Asef2 signaling leads to an overall decrease in Rho activity, which is crucial for stimulating migration and adhesion dynamics. Thus, our results reveal an important new role for Asef2 in promoting cell migration and rapid adhesion turnover by coordinately regulating the activities of Rho-family GTPases.
Background Wound closure accounts for a relatively constant portion of the time required to complete a surgical case. Both longer closure times and wound infections contribute to higher medical costs and patient morbidity.Questions/purposes We therefore determined whether (1) biologic and treatment factors greater influenced wound fhealing than the choice of sutures or staples; and (2) different times to closure affected cost when sutures or staples are used in patients with musculoskeletal tumors. Methods We retrospectively reviewed 511 patients who had sarcoma resections of the buttock, thigh, and femur from 2003 to 2010; 376 had closure with sutures and 135 with staples. Data were abstracted on patient demographics, comorbidities, select procedural data, and wound complications. Wound complications were defined by hospitalization within 6 months postoperatively for a wound problem, irrigation and débridement, or infection treated with antibiotics. We determined the association between staples versus sutures and wound complications after controlling for confounding factors. The minimum followup was 2 weeks. A prospective, timed analysis of wounds closed with either sutures or staples was also performed. Results We found an association between obesity and radiation and wound complications. Wounds were closed an average of 5.3 minutes faster with staples than with suture (0.29 minutes versus 5.6 minutes, respectively), saving a mean 2.1% of the total operating time although the total operating time was similar in the two groups. Conclusions We found no difference in wound complications after closure with sutures or staples, although obesity and radiation treatment appear to affect wound outcomes. Data suggest that time saved in the operating room by closing with staples compensates for added material costs and does not compromise wound care in patients with lower extremity sarcomas.
A 42-year-old man presented with spontaneous ecchymoses of the extremities for the past 2 days and spontaneous epistaxis for the past 2 hours. He had a history of gastroesophageal reflux disease and allergic rhinitis. His medications included esomeprazole, fluticasone nasal spray, and supplemental cholecalciferol. Physical examination revealed multiple ecchymoses on the extremities and abdomen but was otherwise unremarkable. Laboratory evaluation showed a white blood cell countof2.4 × 10 3 /μL,with13%neutrophils,32%lymphocytes,1%monocytes, 0% eosinophils, 0% basophils, and 54% blasts. Hemoglobin level was 10.3 g/dL, and platelet count was 20 × 10 3 /μL. Prothrombin time was 14.5 seconds; international normalized ratio, 1.4; partial thromboplastin time, 27 seconds; D-dimer level, 2.524 μg/mL (13.82 nmol/L); and fibrinogen level, 68 mg/dL (2 μmol/L). A peripheral blood smear was obtained (Figure ). Figure. Peripheral blood smear (Wright-Giemsa, original magnification ×100). WHAT WOULD YOU DO NEXT? A. Administer all-trans retinoic acid (ATRA) after consulting a hematologist B. Administer cytarabine and daunorubicin chemotherapy after consulting a hematologist C. Perform a bone marrow biopsy D. Place a central venous catheter in preparation for replacing blood products Clinical Review & Education
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