Objective. We have investigated whether there is evidence that patients with soft tissue sarcomas do better if treated in a specialist centre compared with district general hospitals.Patients. All patients diagnosed with soft tissue sarcomas who were residents of WMRHA between 1994 and 1996, with minimum follow up of 5 years, excluding head and neck or retroperitoneal tumors.Methods. We reviewed data from the Royal Orthopaedic Hospital Oncology Service (ROHOS) database and the Cancer Intelligence Unit (CIU) Database, with medial record review where necessary. Main outcome measures were local recurrence and overall survival.Results. A total of 260 patients were diagnosed as having STS over the 3-year period (incidence=1.62per 100000 per year): 37% of patients had the majority of treatment at the specialist centre under the care of three surgeons, whilst the other 63% were treated at a total of 38 different hospitals. The rate of local recurrence was 39% at the district general hospitals compared with 19% at the specialist centre despite the fact that tumours treated at the district hospitals were smaller and of lower grade. The most significant factors affecting survival were grade (high versus low) and depth of the tumour. Patients treated at the specialist centre had a small survival advantage after multivariate testing.Conclusion. Soft tissue sarcomas are rare. Centralization of treatment improves local control in all patients and survival in some. Appropriate mechanisms for ensuring that patients with soft tissue sarcomas are seen and treated at specialist centres should be developed.

Nuclear receptor (NR) subfamily 4 group A (NR4A) is a family of three highly homologous orphan nuclear receptors that have multiple physiological and pathological roles, including some in cancer. These NRs are reportedly dysregulated in multiple cancer types, with many studies demonstrating pro-oncogenic roles for NR4A1 (Nur77) and NR4A2 (Nurr1). Additionally, NR4A1 and NR4A3 (Nor-1) are described as tumor suppressors in leukemia. The dysregulation and functions of the NR4A members are due to many factors, including transcriptional regulation, protein-protein interactions, and post-translational modifications. These various levels of intracellular regulation result from the signaling cross-talk of the NR4A members with various signaling pathways, many of which are relevant to cancer and likely explain the family members' functions in oncogenesis and tumor suppression. In this review, we discuss the multiple functions of the NR4A receptors in cancer and summarize a growing body of scientific literature that describes the interconnectedness of the NR4A receptors with various oncogene and tumor suppressor pathways.

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Nuclear receptor subfamily 4 group A member 2 (NR4A2) is an orphan nuclear receptor that is over-expressed in cancer and promotes cell proliferation, migration, transformation, and chemoresistance. Increased expression and function of NR4A2 have been attributed to various signaling pathways, but little is known about microRNA (miRNA) regulation of NR4A2 in cancer. To investigate the posttranscriptional regulation of NR4A2, we used a 3′ untranslated region (UTR) reporter screen and identified miR-34 as a putative regulator of NR4A2. By using computer predictions, we identified and confirmed an miRNA recognition element in the 3′ UTR of NR4A2 that was responsible for miR-34–mediated suppression. We next demonstrated that overexpression of exogenous miR-34 or activation of the p53 pathway, which regulates endogenous miR-34 expression, decreased NR4A2 expression. Consistent with previous reports, overexpression of NR4A2 blocked the induction of p53 target genes, including mir-34a. This was a phenotypic effect, as NR4A2 overexpression could rescue cells from p53-induced inhibition of proliferation. In summary, our results are the first characterization of a cancer-related miRNA capable of regulating NR4A2 and suggest a network and possible feedback mechanism involving p53, miR-34, and NR4A2.