The credibility and creativity of an author may be gauged by the number of scientific papers he or she has published, as well as the frequency of citations of a particular paper reflecting the impact of the data on the area of practice. The object of this study was to identify and analyse the qualities of the top 100 cited papers in orthopaedic surgery. The database of the Science Citation Index of the Institute for Scientific Information (1945 to 2008) was used. A total of 1490 papers were cited more than 100 times, with the top 100 being subjected to further analysis. The majority originated in the United States, followed by the United Kingdom. The top 100 papers were published in seven specific orthopaedic journals. Analysis of the most-cited orthopaedic papers allows us a unique insight into the qualities, characteristics and clinical innovations required for a paper to attain 'classic' status.

Bone marrow derived Mesenchymal Stem Cells (MSCs) are known to specifically migrate to and engraft at tumor sites. Understanding interactions between cancer cells and MSCs has become fundamental to determining whether MSC-tumour interactions should be harnessed for delivery of therapeutic agents or considered a target for intervention. Breast Cancer Cell lines (MDA-MB-231, T47D & SK-Br3) were cultured alone or on a monolayer of MSCs, and retrieved using epithelial specific magnetic beads.Alterations in expression of 90 genes associated with breast tumorgenicity were analyzed using low density array. Expression of markers of Epithelial-Mesenchymal transition and array results were validated using RQ-PCR. Co-cultured cells were analyzed for changes in protein expression, growth pattern, and morphology. Gene expression and proliferation assays were also performed on indirect co-cultures. Following direct co-culture with MSCs, breast cancer cells expressed elevated levels of oncogenes (NCOA4, FOS), protooncogenes (FYN, JUN), genes associated with invasion (MMP11), angiogenesis (VEGF)and anti-apoptosis (IGF1R, BCL2). However, universal downregulation of genes associated with proliferation was observed (Ki67, MYBL2), and reflected in reduced ATP production in response to MSC-secreted factors. Significant upregulation of Epithelial-Mesenchymal Transition specific markers (N-cadherin, Vimentin, Twist and Snail) was also observed following co-culture with MSCs, with a reciprocal downregulation in E-cadherin protein expression. These changes were predominantly cell contact mediated and appeared to be MSC specific. Breast cancer cell morphology and growth pattern also altered in response to MSCs. Mesenchymal Stem Cells may promote breast cancer metastasis through facilitation of Epithelial-Mesenchymal Transition.

This paper's identification of the classic papers of pediatric orthopaedic surgery gives us a unique insight into the development of pediatric orthopaedic surgery in the twentieth and early twenty-first centuries and identifies those individuals who have contributed the most to the body of knowledge used to guide evidence-based clinical decision-making in pediatric orthopaedics today.