No abstract

Ewing sarcoma (ES) is a highly aggressive pediatric cancer that may arise from neuronal precursors. Neurotrophins stimulate neuronal devlopment and plasticity. Here, we found that neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as their receptors (TrkA and TrkB, respectively) are expressed in ES tumors. Treatment with TrkA (GW-441756) or TrkB (Ana-12) selective inhibitors decreased ES cell proliferation, and the effect was increased when the two inhibitors were combined. ES cells treated with a pan-Trk inhibitor, K252a, showed changes in morphology, reduced levels of β-III tubulin, and decreased mRNA expression of NGF, BDNF, TrkA and TrkB. Furthermore, combining K252a with subeffective doses of cytotoxic chemotherapeutic drugs resulted in a decrease in ES cell proliferation and colony formation, even in chemoresistant cells. These results indicate that Trk inhibition may be an emerging approach for the treatment of ES.

Although decreased hip range of motion has been detected in many soccer players with noncontact anterior cruciate ligament (ACL), it is not clear whether it is associated with bone spurs, capsular soft tissue stiffness or both. Our aim was to investigate abnormal radiographic findings in soccer players with limited hip range of motion and noncontact ACL injury. Fifty consecutive male soccer players with restricted hip range of motion and noncontact ACL injury were subjected to radiographic examination to identify bone changes that could be associated with decreased hip range of motion. Of 50 patients, 56% revealed abnormal radiographic findings: pericapsular calcifications or acetabular rim osteophytes (24%), femoral neck deformity (10%), femoral neck and acetabular rim disorders (18%), neck groove caused by impingement (4%). Radiographic evaluation of those individuals showed a high number of bone abnormalities around the hip joint. This was considered to be an important finding to guide a decision-making process between three different approaches: changing the type of sports practiced, undergoing a more restrictive surgery (such as a double-bundle intra-articular reconstruction or an intra plus extra technique) or the onset of a hip-stretching program in addition to the conventional ACL rehabilitation protocol. In this last option, ACL-operated patients without radiographic hip abnormalities may have better outcomes for their decreased hip range of motion when submitted to a stretching program targeting the prevention of rotational overload on the reconstructed intra-articular grafts. The decision-making process concerning soccer players with ACL ruptures should take into consideration the amount of motion-limiting abnormalities around the hip joint.

BackgroundRelapse in localized Ewing sarcoma patients has been a matter of concern regarding poor prognosis. Therefore, we investigated the impact of local control modality (surgery, surgery plus radiotherapy, and radiotherapy) on clinical outcomes such as survival and recurrence in patients with non-metastatic Ewing sarcoma treated on the first Brazilian Collaborative Group Trial of the Ewing Family of Tumors (EWING1).MethodsSeventy-three patients with localized Ewing sarcoma of bone aged < 30 years were included. The treating physicians defined the modality of local control based on the recommendations of the coordinating center and the patient and tumor characteristics. Possible associations of local control modality with local failure (LF), disease-free survival (DFS), event-free survival (EFS), overall survival (OS), and clinical characteristics were analyzed.ResultsMean patient age was 12.8 years (range, 2 to 25 years) and median follow-up time was 4.5 years (range, 2.3 to 6.7 years). Forty-seven patients underwent surgery, 13 received radiotherapy, and 13 received both. The 5-year EFS, OS, and DFS for all patients was 62.1%, 63.3%, and 73.1%, respectively. The 5-year cumulative incidence (CI) of LF was 7.6% for surgery, 11.1% for radiotherapy, and 0% for postoperative radiotherapy (PORT) (p = 0.61). The 5-year EFS was 71.7% for surgery, 30.8% for radiotherapy, and 64.1% for PORT (p = 0.009).ConclusionsThere was a significant effect of local control modality on EFS and OS in the study. Surgery and PORT modalities yielded very close results. The group treated with radiotherapy alone had considerably worse outcomes. This may be confounded by greater risk factors in these patients. There was no significant effect of local control modality on the CI of LF and DFS.