Cabozantinib in neuroendocrine tumours: tackling drug activity and resistance mechanisms

Neuroendocrine tumors (NETs) are highly vascularized malignancies in which angiogenesis may entail cell proliferation and survival. Among the emerging compounds with antivascular properties, cabozantinib (CAB) appeared promising. We analyzed the antitumor activity of CAB against NETs utilizing in vitro and in vivo models. For cell cultures, we used BON-1, NCI-H727 and NCI-H720 cell lines. Cell viability was assessed by manual count coupled with quantification of cell death, performed through fluorescence-activated cell sorting analysis as propidium iodide exclusion assay. In addition, we investigated the modulation of the antiapoptotic myeloid cell leukemia 1 protein under CAB exposure, as a putative adaptive pro-survival mechanism, and compared the responses with sunitinib. The activity of CAB was also tested in mouse and zebrafish xenograft tumor models. Cabozantinib showed a dose-dependent and time-dependent effect on cell viability and proliferation in human NET cultures, besides a halting of cell cycle progression for endoduplication, never reported for other tyrosine kinase inhibitors. In a transplantable zebrafish model, CAB drastically inhibited NET-induced angiogenesis and migration of implanted cells through the embryo body. CAB showed encouraging activity in NETs, both in vitro and in vivo models. On this basis, we envisage future research to further investigate along these promising lines

Editorial: Special Issue “Satellite Networks for Massive IoT Communication”

The growing need to interconnect sensors and devices anytime, anywhere is stimulating the design and development of innovative solutions for efficiently supporting a wide variety of applications: from simple low-duty cycle sensors for which energy efficiency and low-cost are of paramount importance, to more demanding platforms (e [...

S-MIM radio interface for mobile satellite services

An article discussing S-MIM, a novel radio interface for mobile satellite multimedia services. This article should cover the interface’s operating principles; the advanced type of random access used for its transmission; its development, testing, and standardization (in Europe); and its modest transmitter power and high bandwidth efficiency, which allow the use of low-cost user terminals

S-MIM: A Novel Radio Interface for Efficient Messaging Services over Satellite

This article presents a radio interface recently standardized by ETSI under the name of S-band Mobile Interactive Multimedia (S-MIM) and especially designed to provide ubiquitous messaging services over S-band GEO satellites using low-power terminals. Thanks to low terminal cost and high bandwidth efficiency, this standard allows the development of new satellite services, particularly for vehicular and machine-to machine applications. The S-MIM standard relies on a broadcasting radio interface such as DVB-SH or ETSI SDR in the forward link, and reuses 3GPP W-CDMA technology properly adapted to the scope in the return link. Thanks to the use of spread spectrum ALOHA, terminals can access the channel in a totally asynchronous manner. The use of a packet-optimized iterative successive interference cancellation (i- SIC) algorithm at the receiver allows exploiting the inherent power imbalance among terminals in order to boost the throughput with respect to conventional SSA systems. In addition, advanced packet transmission control techniques have been adopted to maximize the probability of successful packet reception in the challenging land mobile satellite channel. Finally, the S-MIM link layer provides efficient and reliable transport of IP datagrams over the forward and return link radio interfaces

On the Modeling and Performance Assessment of Random Access with SIC

In this paper, we review the key figures of merit to assess the performance of advanced random access (RA) schemes exploiting physical layer coding, repetitions and collision resolution techniques. We then investigate RA modeling aspects and their impact on the figures of merit for the exemplary advanced RA schemes: Contention Resolution Diversity Slotted ALOHA (CRDSA), Irregular Repetition Slotted ALOHA (IRSA), Coded Slotted ALOHA (CSA) and Enhanced Spread-Spectrum ALOHA (E-SSA). We show that typical simplifications of the reception model when used to optimize RA schemes lead to inaccurate findings, both in terms of parameter optimization and figures of merit, such as the packet loss ratio (PLR) and throughput. We also derive a generic RA energy efficiency model able to compare the schemes in terms of the energy required to transmit a packet. The combination of achievable RA throughput at the target PLR and energy efficiency, for the same average user power investment per frame and occupied bandwidth, shows that E-SSA, which is an unslotted scheme, provides the best overall performance, while, in terms of the slotted schemes, CRDSA outperforms the more elaborated IRSA and CSA. This surprising results is due to the fact that the IRSA and CSA optimization has so far been performed using RA channel models that are not accurately reflecting the physical layer receiver behavior. We conclude by providing insights on how to include more accurate reception models in the IRSA and CSA design and optimization.Comment: To appear in IEEE Journal on Selected Areas in Communications - Special Issue on Advances in Satellite Communication