BACKGROUND: Previous reports of Ewing sarcoma cohorts suggested that there is a difference in incidence according to racial origin. However, to the authors' knowledge, this finding has never been tested in a population‐based database, and the impact of race on clinical outcome and the significance of known risk factors stratified to racial groups have not been reported. METHODS: Patients who had Ewing sarcoma diagnosed between 1973 and 2005 were identified in the Surveillance, Epidemiology, and End Results database. Patient demographic and clinical characteristics; incidence; year of diagnosis; tumor location, tumor size, and disease stage at diagnosis; treatment(s); cause of death; and survival were extracted. Kaplan‐Meier, log‐rank, and Cox regressions were used to analyze the significance of prognostic factors. RESULTS: Race‐specific incidence indicated that Caucasians have the highest incidence (0.155), followed by Asians/Pacific Islanders (0.082), and African Americans (0.017). The difference in incidence between Caucasians and African Americans was 9‐fold and significant (P < .001). The incidence of Ewing sarcoma increased over the past 3 decades among Caucasians (P < .05). Survival was not impacted by race. Local disease stage, primary tumor location in the appendicular skeleton, and tumor size ≤8 cm conferred a significant survival benefit. Women demonstrated improved survival among the Caucasian patients (P < .03). CONCLUSIONS: To the authors' knowledge, this is the first report focusing on racial disparity in incidence of Ewing sarcoma. Caucasians were affected more frequently, although outcomes were similar between races. It is noteworthy that being a woman constituted a survival benefit only among the Caucasian patients. Further studies will need to clarify the reasons for racial disparities in incidence and for sex differences in survival. Cancer 2009. © 2009 American Cancer Society.

This analysis of a large cohort of adults with PLB indicated that the only identifiable prognostic indicators were localized disease and younger age. The authors concluded that future treatment for patients with PLB need to be based on strict staging criteria and adherence to successful published protocols using collaborative clinical trials.

Matrix remodeling, degradation, inflammation and invasion liberate peptide fragments that can subsequently interact with cells in an attachment-independent manner. Such 'soluble' matrix components, including collagens, fibronectin and laminin, induced Smad activation (termed crosstalk signaling), which follows a similar chronological sequence and R-Smad specificity as induced by transforming growth factor (TGF)-b1. Smad4 nuclear translocation occurred in response to collagen binding, indicating downstream signal propagation. TGF-b scavenging antibody affected only TGF-b1, but not crosstalk-induced responses. TGF-b type II receptor mutation (DR26D25), which is deficient in TGF-b type I receptor recruitment to the ligand, induced a heterotetramer signaling complex, and propagated Smad2 activation only through collagen induction and not TGF-b signaling. Consequentially, TGF-b ligand participation is not required for crosstalk signaling. This signaling requires a functional integrin b1 receptor as showed by RNA interference. Co-immunoprecipitation (co-IP) and fluorescent microscopy indicate the involvement of focal adhesion kinase (FAK) and Src activity in collagen-induced signal propagation, and suggest a membrane signaling complex formation that includes both TGF-b receptors and integrins. The related gene expressional responses are distinct from that evoked by TGF-b1, supporting its separate function. This signaling mechanism expands and partially explains TGFb receptor dynamics and consequential signaling diversityrelated gene expressional plasticity.

Interleukin-6 (IL-6) induces the activation of the Src family kinase Hck, which is associated with the IL-6 receptor ␤-chain, gp130. Here we describe the identification of an "acidic" domain comprising amino acids 771 to 811 of gp130 as a binding region for Hck, which mediates proliferative signaling. The deletion of this region of gp130 (i.e., in deletion mutant d771-811) resulted in a significant reduction of Hck kinase activity and cell proliferation upon stimulation of gp130 compared to wild-type gp130. In addition, d771-811 disrupted the growth factor-stimulated activation of Erk and the dephosphorylation of Pyk2. Based on these findings, we propose a novel, acidic domain of gp130, which is responsible for the activation of Hck, Erk, and Pyk2 and signals cell proliferation upon growth factor stimulation.To exert its biological effects, interleukin-6 (IL-6) must bind to the IL-6 receptor (IL-6R), composed of two ␣-chains (IL-6R␣, 80 kDa) and two ␤-chains (IL-6R␤ or gp130, 130 kDa). Two moieties of IL-6 and two pairs of these receptor chains form a functional hexameric IL-6R complex (42,43,55). The subsequent intracellular signaling events are activated via gp130, which is the common ␤-chain of the receptors for cardiotrophin 1, ciliary neurotrophic factor, oncostatin M, leukemia inhibitory factor, . Activation of the IL-6R stimulates at least two major signaling pathways, the Src homology 2 (SH2) domain containing protein tyrosine phosphatase 2 (Shp-2)/mitogen-activated protein kinase (MAPK) signaling cascade (8,26,31,32,41,46) and the Janus kinase (Jak)/signal transducer and activator of transcription (STAT) pathway (6,18,25,45). It was shown in recent in vivo studies that gp130-mediated signals were regulated by a balance between these two pathways (33). However, the signaling cascades mediating IL-6-induced cell growth are not fully defined. It was shown that Jak and STAT proteins are activated by IL-6 in multiple myeloma (MM) cells independently of the proliferative response. In contrast, MAPK was activated only in cells showing a proliferative response to IL-6 (32). Moreover, the physical separation of gp130 and Shp-2 reduced cell proliferation (26).We have shown previously that at least three members of the Src family of tyrosine kinases, i.e., Fyn, Hck, and Lyn, coprecipitate with gp130 in lysates of MM cells (20). Stimulation of cells with IL-6 increased the activity of these kinases. The association of Hck kinase with gp130 appeared to be stronger than either of the other two kinases. Therefore, we decided to focus on the Hck kinase to elucidate the mechanism(s) and biological significance of the IL-6-mediated Src kinase activation. To identify the gp130 binding domain for Hck, several mutants of gp130 were constructed. These mutants were based on a chimeric receptor consisting of the extracellular part of the erythropoietin receptor (EPOR) and the intracellular part of human gp130 (23). These EPOR/gp130 receptor chimeras (Eg) allowed study of the activation of gp130 by erythropoietin (EPO) after tr...