Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy

High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T). METHODS: In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn. RESULTS: From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344-5.254); P=0.005), maintenance schedule (HR=0.480; (0.246-0.936); P=0.031) and multifocality (HR=2.065; (1.033-4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148-0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death. CONCLUSION: s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy.

Cost Allocation Model for Distribution Networks Considering High Penetration of Distributed Energy Resources

The high penetration of distributed energy resources (DER) in distribution networks and the competitiveenvironment of electricity markets impose the use of new approaches in several domains. The networkcost allocation, traditionally used in transmission networks, should be adapted and used in the distribu-tion networks considering the specifications of the connected resources. The main goal is to develop afairer methodology trying to distribute the distribution network use costs to all players which are usingthe network in each period. In this paper, a model considering different type of costs (fixed, losses, andcongestion costs) is proposed comprising the use of a large set of DER, namely distributed generation(DG), demand response (DR) of direct load control type, energy storage systems (ESS), and electric vehi-cles with capability of discharging energy to the network, which is known as vehicle-to-grid (V2G). Theproposed model includes three distinct phases of operation. The first phase of the model consists in aneconomic dispatch based on an AC optimal power flow (AC-OPF); in the second phase Kirschen’s andBialek’s tracing algorithms are used and compared to evaluate the impact of each resource in the net-work. Finally, the MW-mile method is used in the third phase of the proposed model. A distributionnetwork of 33 buses with large penetration of DER is used to illustrate the application of the proposedmodel.

Cost allocation model for distribution networks considering high penetration of distributed energy resources

The high penetration of distributed energy resources (DER) in distribution networks and the competitive environment of electricity markets impose the use of new approaches in several domains. The network cost allocation, traditionally used in transmission networks, should be adapted and used in the distribution networks considering the specifications of the connected resources. The main goal is to develop a fairer methodology trying to distribute the distribution network use costs to all players which are using the network in each period. In this paper, a model considering different type of costs (fixed, losses, and congestion costs) is proposed comprising the use of a large set of DER, namely distributed generation (DG), demand response (DR) of direct load control type, energy storage systems (ESS), and electric vehicles with capability of discharging energy to the network, which is known as vehicle-to-grid (V2G). The proposed model includes three distinct phases of operation. The first phase of the model consists in an economic dispatch based on an AC optimal power flow (AC-OPF); in the second phase Kirschen's and Bialek's tracing algorithms are used and compared to evaluate the impact of each resource in the network. Finally, the MW-mile method is used in the third phase of the proposed model. A distribution network of 33 buses with large penetration of DER is used to illustrate the application of the proposed model.