Toll-like receptors: New targets for multiple myeloma treatment?

Despite recent biomedical improvements in treating multiple myeloma, this disease still remains incurable. Toll-like receptors (TLRs) are key immune receptors that recognize conserved molecular patterns expressed by pathogens and damaged cells. Activation of TLRs can induce several effects including inflammatory responses, modulation of cell cycle, apoptosis, or regulation of cell metabolism. In multiple myeloma there is a dysregulated signalling of TLRs due to an abnormal presence of certain pathogens and release of molecules from damaged cells. Thus, TLRs could be critical players for tumour microenvironment and multiple myeloma progression. This haematological malignancy is characterized by a high percentage of recurrences, where many patients can develop residual drug-resistant malignant cells. Strategic targeting of TLRs might result in novel therapeutic combinations that improve the response to current treatments, reducing relapses. This review examines the potential of TLRs as targets for the treatment of multiple myeloma, making a particular emphasis on their therapeutic applications

Business scenarios, technical challenges and system requirements - D2.1

Deliverable D2.1 del projecte Europeu OneFIT (ICT-2009-257385)Preprin

Validation platform specification – D5.1

Deliverable D5.1 del projecte Europeu OneFIT (ICT-2009-257385)The present deliverable introduces the OneFIT Proof-of-Concept (PoC) Architecture which will be used as a basis for the validation platform development throughout the project. This PoC Architecture proposal is validated by identifying the roles of the various components in the framework of the OneFIT Scenarios as derived and detailed in WP2. The applied methodology ensures that all required features are appropriately considered. Furthermore, the hardware components available to the project are detailed which are the basis for the development of an integrated validation platform. Their role is highlighted by an instantiation step which maps the PoC Architecture components to the identified hardware components. Finally, a scenario instantiation is derived which illustrates the role of the various hardware components for the validation of selected OneFIT scenarios.Postprint (published version

OneFIT functional and system architecture - D2.2

Deliverable D2.2 del projecte Europeu OneFIT (ICT-2009-257385)This document presents the OneFIT functional and system architecture for the management and control of infrastructure coordinated opportunistic networks (ONs). The most relevant building blocks "Cognitive management System for the Coordination of the Infrastructure" (CSCI) and the "Cognitive Management system for the Opportunistic Network" (CMON) are described.Postprint (published version

Obesity induced alterations in redox homeostasis and oxidative stress are present from an early age.

OBJECTIVES:Oxidative stress and inflammation have been postulated as underlying mechanisms for the development of obesity-related insulin resistance. This association however, remains elusive especially in childhood. We sought to investigate this relation by measuring oxidative stress and antioxidant response biomarkers, before and during an oral glucose tolerance test (OGTT), in different biological samples from obese children. SUBJECTS:24 children were recruited for the study, (18 obese and 6 controls). After OGTT, the obese group was subdivided in two, according to whether or not carbohydrate metabolic impairment (Ob.IR+, Ob.IR-; respectively) was found. Different biomarkers were analyzed after fasting (T = 0) and during an OGTT (T = 60 and 120 min). Lipoperoxides were measured in plasma, erythrocytes, and urine; while advanced glycation end products were determined in plasma, and redox status (GSH/GSSG ratio) in erythrocytes. RESULTS:We found marked differences in the characterization of the oxidative status in urine and erythrocytes, and in the dynamics of the antioxidant response during OGTT. Specifically, Ob.IR+ children show increased oxidative stress, deficient antioxidant response and a significant imbalance in redox status, in comparison to controls and Ob.IR- children. CONCLUSION:Obese children with insulin resistance show increased levels of oxidative stress biomarkers, and a stunted antioxidant response to an OGTT leading to increased oxidative stress after a single glucose load, as detected in erythrocytes, but not in plasma. We propose erythrocytes as sensors of early and acute changes in oxidative stress associated with insulin resistance in childhood obesity. This is a pilot study, performed with a limited sample size, so data should be interpreted with caution until reproduced

Characteristics of study population.

<p>Characteristics of study population.</p

Redox status in RBC of healthy and obese children before and along an OGTT.

<p>(A) Total glutathione concentration (sum of all glutathione equivalents or tGSH, and (B) Reduced glutathione/oxidized glutathione rate, as measured in RBCs, at baseline and along the OGTT. White bars represent the control group, grey bars represent Ob.IR- group, and black bars represent Ob.IR+ group. Data are represented as mean ± SEM. P<0.05 was considered for statistical significance. (a) show significant differences relative to control at baseline, (b) shows significant differences relative to Ob.IR-, and (#) intragroup differences along the OGTT compared to baseline values.</p

Total antoxiodant capacity (TAC) in venous blood in control and obese children.

<p>(A) Plasmatic TAC and, (B) RBC’s TAC at baseline and along 75 g. OGTT. White bars represent the control group, grey bars represent Ob.IR- group, and black bars represent Ob.IR+ group. Data are represented as mean ± SEM. P<0.05 was considered for statistical significance. (a) show significant differences relative to control at baseline, (b) shows significant differences relative to Ob.IR-, and (#) intragroup differences along the OGTT compared to baseline values.</p

Plasmatic Advanced Glycation End Products (AGEs) in control and obese children.

<p>Measured at baseline and along the OGTT. Data is expressed in μg of CML/ml. White bars represent the control group, grey bars represent Ob.IR- group, and black bars represent Ob.IR+ group. Data are represented as mean ± SEM. P<0.05 was considered for statistical significance. (a) show significant differences relative to control at baseline, (b) shows significant differences relative to Ob.IR-, and (#) intragroup differences along the OGTT respect to baseline values.</p

Catalase activity in RBC of healthy and obese children.

<p>At baseline and along the OGTT. Data is expressed in nmol H₂O₂ x min^-1 x mg^-1 of protein. White bars represent the control group, grey bars represent Ob.IR- group, and black bars represent Ob.IR+ group. Data are represented as mean ± SEM. P<0.05 was considered for statistical significance. (a) show significant differences relative to control at baseline, (b) shows significant differences relative to Ob.IR-, and (#) intragroup differences along the OGTT compared to baseline values.</p