Experimental SDN Control Solutions for Automatic Operations and Management of 5G Services in a Fixed Mobile Converged Packet-Optical Network

5G networks will impose network operators to accommodate services demanding heterogeneous and stringent requirements in terms of increased bandwidth, reduced latency, higher availability, etc. as well as enabling emerging capabilities such as slicing. Operators will be then forced to make notable investments in their infrastructure but the revenue is not envisaged to be proportional. Thereby, operators are seeking for more cost-effective solutions to keep their competitiveness. An appealing solution is to integrate all (broadband) services including both fixed and mobile in a convergent way. This is referred to as Fixed Mobile Convergence (FMC). FMC allows seamlessly serving any kind of access service over the same network infrastructure (access, aggregation and core) and relying on common set of control and operation functions. To this end, FMC leverages the benefits provided by Software Defined Networking (SDN) and Network Function Virtualization (NFV). First, we discuss some of the explored FMC solutions and technologies, from both structural and functional perspectives Next, focusing on a Multi-Layer (Packet and Optical) Aggregation Network, we report two implemented and experimentally validated SDN/NFV orchestration architectures providing feasibleThis work has been partially funded by the Spanish Ministry MINECO projects DESTELLO (TEC2015-69256-R) and 5G-REFINE (TEC2017-88373-R), and the EU H2020 5G TRANSFORMER project (grant no. 761536)

uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy

There is strong evidence supporting the role of the plasminogen activator system in head and neck squamous cell carcinoma (HNSCC), particularly of its uPA (urokinase plasminogen activator) / uPAR (urokinase plasminogen activator receptor) and SERPINE1 components. Overexpression of uPA/uPAR and SERPINE1 enhances tumor cell migration and invasion and plays a key role in metastasis development, conferring poor prognosis. The apparent paradox of uPA/uPAR and its inhibitor SERPINE1 producing similar effects is solved by the identification of SERPINE1 activated signaling pathways independent of uPA inhibition. Both uPA/uPAR and SERPINE1 are directly linked to the induction of epithelial-to-mesenchymal transition, the acquisition of stem cell properties and resistance to antitumor agents. The aim of this review is to provide insight on the deregulation of these proteins in all these processes. We also summarize their potential value as prognostic biomarkers or potential drug targets in HNSCC patients. Concomitant overexpression of uPA/uPAR and SERPINE1 is associated with a higher risk of metastasis and could be used to identify patients that would benefit from an adjuvant treatment. In the future, the specific inhibitors of uPA/uPAR and SERPINE1, which are still under development, could be used to design new therapeutic strategies in HNSCCs

A novel orally available inhibitor of focal adhesion signaling increases survival in a xenograft model of diffuse large B-cell lymphoma with central nervous system involvement

Central nervous system dissemination is a relatively uncommon but almost always fatal complication in diffuse large B-cell lymphoma patients. Optimal therapy for central nervous involvement in this malignancy has not been established. In this paper, we aimed to evaluate the therapeutic effect of E7123, a celecoxib derivative that inhibits focal adhesion signaling, in a novel xenograft model of diffuse large B-cell lymphoma with central nervous system involvement. Cells obtained after disaggregation of HT subcutaneous tumors (HT-SC cells) were intravenously injected in NOD/SCID mice. These mice received oral vehicle or 75 mg/kg of E7123 daily until they were euthanized for weight loss or signs of sickness. The antitumor effect of E7123 was validated in an independent experiment using a bioluminescent mouse model. Intravenously injected HT-SC cells showed higher take rate and higher central nervous system tropism (associated with increased expression of beta 1-integrin and p130Cas proteins) than HT cells. The oral administration of E7123 significantly increased survival time in 2 independent experiments using mice injected with unmodified or bioluminescent HT-SC cells. We have developed a new xenograft model of diffuse large B-cell lymphoma with central nervous system involvement that can be used in the pre-clinical evaluation of new drugs for this malignancy. E7123 is a new, well-tolerated and orally available therapeutic agent that merits further investigation since it may improve current management of diffuse large B-cell lymphoma patients with central nervous system involvement

Experimental framework and evaluation of the 5G-Crosshaul Control Infrastructure

The goal of 5G-Crosshaul is to integrate fronthaul and backhaul operation under the same data and controlplanes. This paper focuses on the latter, by experimentally showing theflexibility of the 5G-Crosshaul ControlInfrastructure (XCI). In this sense, various network setups featuring heterogeneous network and computingresources and high-speed mobility were deployed over the 5G-Crosshaul testbed. More specifically, three dif-ferent use cases that exploit the capabilities embedded in the XCI have been experimentally evaluated. First,"hierarchical network orchestration" demonstrates how service setup times in complex multi-technology trans-port networks can be decreased from current manual configuration times in the order of days down to automatedsetups in the order of seconds by means of a resource management application that consumes the XCI services.Second, "energy management of IT and network resources" presents an energy management application thatexploits the XCI to deploy network configurations that achieve energy savings ranging from 15% to 40% bydynamically reacting to datacenter and network conditions. Finally, the XCI was also exploited by an energy management application in a high-speed train mobility scenario featuring a radio over fiber network in which savings close to 80% were achieved

Novel Resource and Energy Management for 5G Integrated Backhaul/Fronthaul (5G-Crosshaul)

The integration of both fronthaul and backhaul into a single transport network (namely, 5G-Crosshaul) is envisioned for the future 5G transport networks. This requires a fully integrated and unified management of the fronthaul and backhaul resources in a cost-efficient, scalable and flexible way through the deployment of an SDN/NFV control framework. This paper presents the designed 5G-Crosshaul architecture, two selected SDN/NFV applications targeting for cost-efficient resource and energy usage: the Resource Management Application (RMA) and the Energy Management and Monitoring Application (EMMA). The former manages 5G-Crosshaul resources (network, computing and storage resources). The latter is a special version of RMA with the focus on the objectives of optimizing the energy consumption and minimizing the energy footprint of the 5G-Crosshaul infrastructure. Besides, EMMA is applied to the mmWave mesh network and the high speed train scenarios. In particular, we present the key application design with their main components and the interactions with each other and with the control plane, and then we present the proposed application optimization algorithms along with initial results. The first results demonstrate that the proposed RMA is able to cost-efficiently utilize the Crosshaul resources of heterogeneous technologies, while EMMA can achieve significant energy savings through energy-efficient routing of traffic flows. For experiments in real system, we also set up Proof of Concepts (PoCs) for both applications in order to perform real trials in the field.© 2017 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works

Higher metastatic efficiency of KRas G12V than KRas G13D in a colorectal cancer model

Although all KRas (protein that in humans is encoded by the KRas gene) point mutants are considered to have a similar prognostic capacity, their transformation and tumorigenic capacities vary widely. We compared the metastatic efficiency of KRas G12V (Kirsten rat sarcoma viral oncogene homolog with valine mutation at codon 12) and KRas G13D (Kirsten rat sarcoma viral oncogene homolog with aspartic mutation at codon 13) oncogenes in an orthotopic colorectal cancer (CRC) model. Following subcutaneous preconditioning, recombinant clones of the SW48 CRC cell line [Kras wild-type (Kras WT)] expressing the KRas G12V or KRas G13D allele were microinjected in the mouse cecum. The percentage of animals developing lymph node metastasis was higher in KRas G12V than in KRas G13D mice. Microscopic, macroscopic, and visible lymphatic foci were 1.5- to 3.0-fold larger in KRas G12V than in KRas G13D mice (P < 0.05). In the lung, only microfoci were developed in both groups. KRas G12V primary tumors had lower apoptosis (7.0 ± 1.2 vs. 7.4 ± 1.0 per field, P = 0.02), higher tumor budding at the invasion front (1.2 ± 0.2 vs. 0.6 ± 0.1, P = 0.04), and a higher percentage of C-X-C chemokine receptor type 4 (CXCR4)-overexpressing intravasated tumor emboli (49.8 ± 9.4% vs. 12.8 ± 4.4%, P < 0.001) than KRas G13D tumors. KRas G12V primary tumors showed Akt activation, and β5 integrin, vascular endothelial growth factor A (VEGFA), and Serpine-1 overexpression, whereas KRas G13D tumors showed integrin β1 and angiopoietin 2 (Angpt2) overexpression. The increased cell survival, invasion, intravasation, and specific molecular regulation observed in KRas G12V tumors is consistent with the higher aggressiveness observed in patients with CRC expressing this oncogene

uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy

There is strong evidence supporting the role of the plasminogen activator system in head and neck squamous cell carcinoma (HNSCC), particularly of its uPA (urokinase plasminogen activator) / uPAR (urokinase plasminogen activator receptor) and SERPINE1 components. Overexpression of uPA/uPAR and SERPINE1 enhances tumor cell migration and invasion and plays a key role in metastasis development, conferring poor prognosis. The apparent paradox of uPA/uPAR and its inhibitor SERPINE1 producing similar effects is solved by the identification of SERPINE1 activated signaling pathways independent of uPA inhibition. Both uPA/uPAR and SERPINE1 are directly linked to the induction of epithelial-to-mesenchymal transition, the acquisition of stem cell properties and resistance to antitumor agents. The aim of this review is to provide insight on the deregulation of these proteins in all these processes. We also summarize their potential value as prognostic biomarkers or potential drug targets in HNSCC patients. Concomitant overexpression of uPA/uPAR and SERPINE1 is associated with a higher risk of metastasis and could be used to identify patients that would benefit from an adjuvant treatment. In the future, the specific inhibitors of uPA/uPAR and SERPINE1, which are still under development, could be used to design new therapeutic strategies in HNSCCs

Cancer-specific uptake of a liganded protein nanocarrier targeting aggressive CXCR4⁺ colorectal cancer models

Unliganded drug-nanoconjugates accumulate passively in the tumor whereas liganded nanoconjugates promote drug internalization in tumor cells via endocytosis and increase antitumor efficacy. Whether or not tumor cell internalization associates with enhanced tumor uptake is still under debate. We here compared tumor uptake of T22-GFP-H6, a liganded protein carrier targeting the CXCR4 receptor, and the unliganded GFP-H6 carrier in subcutaneous and metastatic colorectal cancer models. T22-GFP-H6 had a higher tumor uptake in primary tumor and metastatic foci than GFP-H6, with no biodistribution or toxicity on normal tissues. T22-GFP-H6 was detected in target CXCR4+ tumor cell cytosol whereas GFP-H6 was detected in tumor stroma. SDF1-α co-administration switched T22-GFP-H6 internalization from CXCR4+ tumor epithelial cells to the stroma. Therefore, the incorporation of a targeting ligand promotes selective accumulation of the nanocarrier inside target tumor cells while increasing whole tumor uptake in a CXCR4-dependent manner, validating T22-GFP-H6 as a CXCR4-targeted drug carrier

Towards an SDN/NFV-based multi-tenant network and cloud testbed for end-to-end 5G services

5G has a main requirement of highly flexible, ultralow latency and ultra-high bandwidth virtualized infrastructure in order to deliver end-to-end services. This requirement can be met by efficiently integrating all network segments (radio access, aggregation and core) with heterogeneous wireless and optical technologies (5G, mmWave, LTE/LTE-A, Wi-Fi, Ethernet, MPLS, WDM, software-defined optical transmission, etc.), and massive computing and storage cloud services (offered in edge/core data centers, and even, distributed in network nodes). This paper introduces the preliminary architecture aiming at integrating three consolidated and standalone experimental infrastructures at CTTC, in order to deploy the required end-toend top-to-bottom converged infrastructure pointed out above for testing and developing advanced 5G services. The existing experimental facilities cover complementary technologies from terminals to radio access, aggregation/core and cloud, and are: the GEDOMIS R testbed (LTE/5G PHY testbed), the EXTREME Testbed R (wireless HetNet and backhaul, edge datacenter, a d distributed computing nodes), and the ADRENALINE Testbed R (packet aggregation and optical core network, core data-center). Two uses cases addressing Fixed Mobile Convergence (FMC) developed in ADRENALINE and EXTREME, and virtual mobile network function splitting and deployment, involving EXTREME and GEDOMIS, are also presented