IntroductionMetastatic breast cancer cells frequently and ectopically express the transcription factor RUNX2, which normally attenuates proliferation and promotes maturation of osteoblasts. RUNX2 expression is inversely regulated with respect to cell growth in osteoblasts and deregulated in osteosarcoma cells.MethodsHere, we addressed whether the functional relationship between cell growth and RUNX2 gene expression is maintained in breast cancer cells. We also investigated whether the aberrant expression of RUNX2 is linked to phenotypic parameters that could provide a selective advantage to cells during breast cancer progression.ResultsWe find that, similar to its regulation in osteoblasts, RUNX2 expression in MDA-MB-231 breast adenocarcinoma cells is enhanced upon growth factor deprivation, as well as upon deactivation of the mitogen-dependent MEK-Erk pathway or EGFR signaling. Reduction of RUNX2 levels by RNAi has only marginal effects on cell growth and expression of proliferation markers in MDA-MB-231 breast cancer cells. Thus, RUNX2 is not a critical regulator of cell proliferation in this cell type. However, siRNA depletion of RUNX2 in MDA-MB-231 cells reduces cell motility, while forced exogenous expression of RUNX2 in MCF7 cells increases cell motility.ConclusionsOur results support the emerging concept that the osteogenic transcription factor RUNX2 functions as a metastasis-related oncoprotein in non-osseous cancer cells.
Trauma and orthopaedics is the largest of the surgical specialties and yet attracts a disproportionately small fraction of available national and international funding for health research. With the burden of musculoskeletal disease increasing, high-quality research is required to improve the evidence base for orthopaedic practice. Using the current research landscape in the United Kingdom as an example, but also addressing the international perspective, we highlight the issues surrounding poor levels of research funding in trauma and orthopaedics and indicate avenues for improving the impact and success of surgical musculoskeletal research.
Objective
We present data from our recently completed study that suggests that joint salvage is the key parameter in keeping the limb salvage ethos relevant.
Methods
We reviewed all patients operated on nationally over 30 years (1978 to 2008). We identified 265 survivors of which 162 were available for evaluation at the time of survey.
Results
There were 92 males and 70 females followed an average 9.1±SD3.1 years. Average age at survey was 38±SD17 years. ANOVA for mental health and TESS degree of importance for ADL identified that all categories of joint preservation were similar to an average group of people from the population. Physical health scores were significantly better amongst joint‐preserved versus joint replacement patients (p = 0.003). Nevertheless, there was no significant difference between amputees with respect to physical health scores compared to arthrodesed and joint‐replaced individuals. Biological reconstructions scored significantly better than metallic segmentary reconstructions (p < 0.001). Dissatisfaction appeared to correlate best with the presence of pain following reconstruction (p < 0.001).
Conclusions
While our study supports the finding of amputations being as satisfactory as arthrodeses and joint replacement salvage surgery, joint salvage was superior to all other categories. Assessments of equivalence should incorporate joint salvage and materials used as evaluable parameters.
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