What is the impact of local control in Ewing sarcoma: analysis of the first Brazilian collaborative study group-EWING1

Background: Relapse 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). Methods: Seventy-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. Results: Mean 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). Conclusions: There 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.Children's Cancer InstituteRafael Accordi Foundation, Porto Alegre, RS, BrazilHCPA, Serv Orthoped & Traumatol, Rua Ramiro Barcelos 2350, BR-90035903 Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, HCPA, Dept Pediat, Porto Alegre, RS, BrazilPontificia Univ Catolica Rio Grande Sul PUCRS, Dept Pediat, Hosp Sao Lucas, Porto Alegre, RS, BrazilHCPA, Serv Orthoped & Traumatol, Porto Alegre, RS, BrazilUniv Fed Sao Paulo UNIFESP, Support Grp Children & Adolescents Canc GRAACC, Sao Paulo, SP, BrazilHosp Canc Infantojuvenil, Fundacao Pio 12, Barretos, SP, BrazilCtr Hosp Pereira Rossell, Montevideo, UruguayHosp AC Camargo Canc Ctr, Orthoped Serv, Sao Paulo, SP, BrazilSanta Casa Misericordia Porto Alegre, Serv Orthoped & Traumatol, Porto Alegre, RS, BrazilUniv Sao Paulo, Orthoped Trauma Inst, Hosp Clin Sao Paulo, Sch Med, Sao Paulo, SP, BrazilSanta Casa Misericordia Sao Paulo HSCSP, Dept Orthoped & Traumatol, Sao Paulo, SP, BrazilPontificia Univ Catolica Rio Grande Sul PUCRS, Hosp Sao Lucas, Serv Orthoped & Traumatol, Porto Alegre, RS, BrazilUniv Estadual Paulista UNESP, Hosp Clin Botucatu, Sch Med, Botucatu, SP, BrazilInst Canc Infantil, Porto Alegre, RS, BrazilUniv Fed Sao Paulo UNIFESP, Support Grp Children & Adolescents Canc GRAACC, Sao Paulo, SP, BrazilChildren's Cancer InstituteRafael Accordi Foundation, Porto Alegre, RS, BrazilWeb of Scienc

The Brucella effector BspL targets the ER-associated degradation (ERAD) pathway and delays bacterial egress from infected cells

Perturbation of the endoplasmic reticulum (ER), a central organelle of the cell, can have critical consequences for cellular homeostasis. An elaborate surveillance system known as ER quality control ensures that cells can respond and adapt to stress via the unfolded protein response (UPR) and that only correctly assembled proteins reach their destination. Interestingly, several bacterial pathogens hijack the ER to establish an infection. However, it remains poorly understood how bacterial pathogens exploit ER quality-control functions to complete their intracellular cycle. Brucella spp. replicate extensively within an ER-derived niche, which evolves into specialized vacuoles suited for exit from infected cells. Here we present Brucella-secreted protein L (BspL), a Brucella abortus effector that interacts with Herp, a central component of the ERassociated degradation (ERAD) machinery. We found that BspL enhances ERAD at the late stages of the infection. BspL targeting of Herp and ERAD allows tight control of the kinetics of autophagic Brucella-containing vacuole formation, delaying the last step of its intracellular cycle and cell-to-cell spread. This study highlights a mechanism by which a bacterial pathogen hijacks ERAD components for fine regulation of its intracellular trafficking.SCOPUS: ar.jinfo:eu-repo/semantics/publishe