Mean-field sparse Jurdjevic-Quinn control

International audienceWe consider nonlinear transport equations with non-local velocity, describing the time-evolution of a measure, which in practice may represent the density of a crowd. Such equations often appear by taking the mean-field limit of finite-dimensional systems modelling collective dynamics. We first give a sense to dissipativity of these mean-field equations in terms of Lie derivatives of a Lyapunov function depending on the measure. Then, we address the problem of controlling such equations by means of a time-varying bounded control action localized on a time-varying control subset with bounded Lebesgue measure (sparsity space constraint). Finite-dimensional versions are given by control-affine systems, which can be stabilized by the well known Jurdjevic–Quinn procedure. In this paper, assuming that the uncontrolled dynamics are dissipative, we develop an approach in the spirit of the classical Jurdjevic–Quinn theorem, showing how to steer the system to an invariant sublevel of the Lyapunov function. The control function and the control domain are designed in terms of the Lie derivatives of the Lyapunov function, and enjoy sparsity properties in the sense that the control support is small. Finally, we show that our result applies to a large class of kinetic equations modelling multi-agent dynamics

Recent results of cetuximab use in the treatment of squamous cell carcinoma of the head and neck

Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth factor receptor. The role of cetuximab is paramount in several subsets of head and neck cancer. In particular, the EXTREME study has indicated cetuximab as the only drug to improve survival when associated with cisplatin and 5-fluorouracil in patients with recurrent/metastatic disease. Furthermore, cetuximab, both alone and in combination with cisplatin, is active in patients with recurrent/metastatic disease who have failed prior platinum-based chemotherapy. Cetuximab, given in association with radiation therapy, is a treatment of choice in first-line therapy of patients with locally advanced inoperable disease. In the same setting, the role of induction chemotherapy has gained considerable interest over the last few years and a number of efforts are being pursued to optimally integrate induction chemotherapy with radiation therapy plus cetuximab. The combination of cetuximab and other targeted therapies is among the most promising new perspectives for patients with head and neck cancer

Electrochemotherapy as palliative treatment in patients with advanced head and neck tumours: Outcome analysis in 93 patients treated in a single institution.

Abstract Purpose To describe outcomes of Electrochemotherapy as palliative treatment in patients with advanced head and neck (H&N) tumours. Methods Ninety-three patients (120 treatment sessions) with H&N recurrent and/or metastatic neoplasm were treated. Treatment response was assessed 4 weeks after ECT with clinical examination and two months after the first evaluation with a CT scan of the H&N for deep lesions evaluation. The grade of bleeding and pain before, at the end of treatment and one week after ECT were evaluated. Results Five percent of complete responses, 40% of partial responses were registered. Disease progression was seen in 20% of patients after the first ECT procedure, the remaining 34% of patients experienced stable disease. A good control of pain and bleeding was obtained, especially in patients with moderate symptoms before the treatment. No toxicities related to ECT were seen. Conclusions ECT is an interesting antitumoral therapy in advanced chemo and radio-refractory H&N neoplasms. ECT is able to reduce frequent symptoms, such as pain and bleeding, improving quality of life without damage to healthy tissue and with limited side effects. Moreover, ECT reduces hospitalization time and may contribute to an overall reduction in healthcare costs associated with advanced H&N cancers care

Valproic Acid Synergizes With Cisplatin and Cetuximab in vitro and in vivo in Head and Neck Cancer by Targeting the Mechanisms of Resistance

Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a devastating malignancy with a poor prognosis. The combination of cisplatin (CDDP) plus cetuximab (CX) is one of the standard first-line treatments in this disease. However, this therapeutic regimen is often associated with high toxicity and resistance, suggesting that new combinatorial strategies are needed to improve its therapeutic index. In our study, we evaluated the antitumor effects of valproic acid (VPA), a well-known antiepileptic agent with histone deacetylase inhibitory activity, in combination with CDDP/CX doublet in head and neck squamous cell carcinoma (HNSCC) models. We demonstrated, in HNSCC cell lines, but not in normal human fibroblasts, that simultaneous exposure to equitoxic doses of VPA plus CDDP/CX resulted in a clear synergistic antiproliferative and pro-apoptotic effects. The synergistic antitumor effect was confirmed in four different 3D-self-assembled spheroid models, suggesting the ability of the combined approach to affect also the cancer stem cells compartment. Mechanistically, VPA enhanced DNA damage in combination treatment by reducing the mRNA expression of ERCC Excision Repair 1, a critical player in DNA repair, and by increasing CDDP intracellular concentration via upregulation at transcriptional level of CDDP influx channel copper transporter 1 and downregulation of the ATPAse ATP7B involved in CDDP-export. Valproic acid also induced a dose-dependent downregulation of epidermal growth factor receptor (EGFR) expression and of MAPK and AKT downstream signaling pathways and prevent CDDP- and/or CX-induced EGFR nuclear translocation, a well-known mechanism of resistance to chemotherapy. Indeed, VPA impaired the transcription of genes induced by non-canonical activity of nuclear EGFR, such as cyclin D1 and thymidylate synthase. Finally, we confirmed the synergistic antitumor effect also in vivo in both heterotopic and orthotopic models, demonstrating that the combined treatment completely blocked HNSCC xenograft tumors growth in nude mice. Overall, the introduction of a safe and generic drug such as VPA into the conventional treatment for R/M HNSCC represents an innovative and feasible antitumor strategy that warrants further clinical evaluation. A phase II clinical trial exploring the combination of VPA and CDDP/CX in R/M HNSCC patients is currently ongoing in our institute

Sparse Jurdjevic–Quinn stabilization of dissipative systems

International audienceFor control-affine systems with a proper Lyapunov function, the classical Jurdjevic-Quinn procedure gives a well-known and widely used method for the design of feedback controls that asymptotically stabilize the system to some invariant set. In this procedure, all controls are in general required to be activated, i.e. nonzero, at the same time.In this paper we give sufficient conditions under which this stabilization can be achieved by means of sparse feedback controls, i.e., feedback controls having the smallest possible number of nonzero components. We thus obtain a sparse version of the classical Jurdjevic-Quinn theorem.We propose three different explicit stabilizing control strategies, depending on the method used to handle possible discontinuities arising from the definition of the feedback:a time-varying periodic feedback, a sampled feedback, and a hybrid hysteresis. We illustrate our results by applying them to opinion formation models, thus recovering and generalizing former results for such models