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Sean Scully

Publications and source records attributed to Sean Scully.

3 recordsLinked to original sources

Current etiologies and modes of failure in total knee arthroplasty revision.

UNLABELLED: Although total knee arthroplasty is a very effective intervention and increasing in prevalence, failures do occur. We studied patients presenting for total knee arthroplasty revision to determine any modifiable causes of failure, both short and long term, and where future efforts should be directed to reduce the incidence of failure. A multicenter prospective observational cohort study of 318 consecutive patients, with minimum 1 year follow-up, undergoing total knee arthroplasty revision was performed. Associations between modes of failure were also assessed. The mean time from primary procedure to total knee arthroplasty revision was 7.9 years. Many patients (64.4%) had more than one cause of failure. Thirty-one percent of patients were early (< 2 years) failures at a mean of 11 months. These had a higher prevalence of infection, perioperative factors and comorbidities. Late failures occurred at a mean of 119.2 months. Other major causes of failure included instability (28.9%), wear (24.5%) and component loosening suggesting the importance of modifications in technique, implants and other areas. Application of these findings will ultimately reduce revision numbers through continued refinement of total knee arthroplasty practice and through further specific investigation of these modes of failure. LEVEL OF EVIDENCE: Therapeutic study, level II-2 (prospective study). See the Guidelines for Authors for a complete description of levels of evidence.

Adult↗

Activated Src increases adhesion, survival and alpha2-integrin expression in human breast cancer cells.

Focal adhesion kinase (FAK) is an intracellular kinase that localizes to focal adhesions. FAK is overexpressed in human tumours, and FAK regulates both cellular adhesion and anti-apoptotic survival signalling. Disruption of FAK function by overexpression of the FAK C-terminal domain [FAK-CD, analogous to the FRNK (FAK-related non-kinase) protein] leads to loss of adhesion and apoptosis in tumour cells. We have shown that overexpression of an activated form of the Src tyrosine kinase suppressed the loss of adhesion induced by dominant-negative; adenoviral FAK-CD and decreased the apoptotic response in BT474 and MCF-7 breast cancer cell lines. This adhesion-dependent apoptosis was increased by the Src-family kinase inhibitor PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine]. We have also shown that expression of activated Src in breast cancer cells increased the expression of alpha2-integrin and that overexpression of alpha2-integrin suppressed FAK-CD-mediated loss of adhesion. Our results suggest a model in which Src regulates adhesion and survival through enhanced expression of the alpha2-integrin. This provides a mechanism through which Src promotes cellular adhesion and alters the adhesive function of FAK.

Apoptosis↗