Targeted therapies in breast cancer:New challenges to fight against resistance

Breast cancer is the most common type of cancer found in women and today represents a significant challenge to public health. With the latest breakthroughs in molecular biology and immunotherapy, very specific targeted therapies have been tailored to the specific pathophysiology of different types of breast cancers. These recent developments have contributed to a more efficient and specific treatment protocol in breast cancer patients. However, the main challenge to be further investigated still remains the emergence of therapeutic resistance mechanisms, which develop soon after the onset of therapy and need urgent attention and further elucidation. What are the recent emerging molecular resistance mechanisms in breast cancer targeted therapy and what are the best strategies to apply in order to circumvent this important obstacle? The main scope of this review is to provide a thorough update of recent developments in the field and discuss future prospects for preventing resistance mechanisms in the quest to increase overall survival of patients suffering from the disease.

Pathobiology of the neutrophil-intestinal epithelial cell interaction:Role in carcinogenesis

The role of chronic inflammation,acting as an independent factor,on the onset of gastrointestinal carcinogenesis is now well accepted.However,even if there is an increase in the number of elements directly involving polymorphonuclear leukocytes (PMNL),as a major actor in digestive carcinogenesis,the different cellular and molecular events occurring in this process are still not completely understood.The transepithelial migration of PMNL,which is the ultimate step of the afflux of PMNL into the digestive mucosa,is a complex phenomenon involving sequential interaction of molecules expressed both on PMNL and on digestive epithelial cells.Chronic inflammatory areas rich in PMNL [so-called (chronic active inflammation)] and iterative transepithelial migration of PMNL certainly evoke intracellular signals,which lead toward progressive transformation of epithelia.Among these different signals,the mutagenic effect of reactive oxygen species and nitrates,the activation of the nuclear factor-κB pathway,and the modulation of expression of certain microRNA are key actors.Following the initiation of carcinogenesis,PMNL are involved in the progression and invasion of digestive carcinomas,with which they interact.It is noteworthy that different subpopulations of PMNL,which can have some opposite effects on tumor growth,in association with different levels of transforming growth factor-β and with the number of CD8 positive T lymphocytes,could be present during the development of digestive carcinoma.Other factors that involve PMNL,such as massive elastase release,and the production of angiogenic factors,can participate in the progression of neoplastic cells through tissues.PMNL may play a major role in the onset of metastases,since they allow the tumor cells to cross the endothelial barrier and to migrate into the blood stream.Finally,PMNL play a role,alone or in association with other cell parameters,in the initiation,promotion,progression and dissemination of digestive carcinomas.This review focuses on the main currently accepted cellular and molecular mechanisms that involve PMNL as key actors in digestive carcinogenesis.

Regulation of the m RNA half-life in breast cancer

The control of the half-life of m RNA plays a central role in normal development and in disease progression. Several pathological conditions, such as breast cancer, correlate with deregulation of the half-life of m RNA encoding growth factors, oncogenes, cell cycle regulators and inflammatory cytokines that participate in cancer. Substantial stability means that a m RNA will be available for translation for a longer time, resulting in high levels of protein gene products, which may lead to prolonged responses that subsequently result in over-production of cellular mediators that participate in cancer. The stability of these m RNA is regulated at the 3'UTR level by different mechanisms involving m RNA binding proteins, micro-RNA, long non-coding RNA and alternative polyadenylation. All these events are tightly interconnected to each other and lead to steady state levels of target m RNAs. Compelling evidence also suggests that both m RNA binding proteins and regulatory RNAswhich participate to m RNA half-life regulation may be useful prognostic markers in breast cancers, pointing to a potential therapeutic approach to treatment of patients with these tumors. In this review, we summarize the main mechanisms involved in the regulation of m RNA decay and discuss the possibility of its implication in breast cancer aggressiveness and the efficacy of targeted therapy.

Overview of embryonal rhabdomyosarcoma of cervix in women over 40-year-old

The literature on cervical embryonal rhabdomyosarcoma(RMS) is reviewed here to identify management guidelines for middle-aged women diagnosed with this rare type of gynecologic cancer. Specifically, the Pub Med, Web of Science and Google Scholar databases, were searched to find published case series on cervical embryonal RMS reporting on four or more patients, of whom at least one was > 40-year-old. The χ2 test was used to assess heterogeneity. Five articles published between 1986 and 2013 were identified, reporting on a total of 47 patients, of whom 22(46.8%) were older and 25(53.2%) younger than 40-year-old. Although the two age groups did not differ significantly by stage of disease or radiotherapy treatment, the older age groupreceived less chemotherapy(55% vs 90%, P = 0.008)and had more hysterectomy(86% vs 43%, P = 0.009).Follow-up data was missing for 18/47(38.3%) patients.Among the 29 patients with follow-up data, survival was shorter in the older group, with 8/12(67%) alive and3 with disease at a median follow-up of 2.6 years, as compared with the younger group that had 15/17(88%)alive and none with disease at a median follow-up of 3.5years. The longest survivals among the older women were observed in those who received radiotherapy,including one case with a resected lung metastasis.A prospective multi-institutional collaboration and better follow-up are needed to determine the optimal management of cervical embryonal RMS. Long-term survival appears feasible if management is accompanied by chemotherapy and radiotherapy.

A Joint Mobility Management Approach and Data Rate Adaptation Algorithm for IEEE 802.15.4/ZigBee Nodes

This paper presents an original approach to reduce energy consumption in an IEEE 802.15.4/ZigBee cluster tree network related to a backbone network. Our approach uses an enhanced mobility management of end devices combined with a rate adaptation algorithm. The mobility management approach anticipates link disruption and relies on a speculative algorithm that does not require scanning neighbor cells. The joint mobility management and rate adaptation methods are based on the link quality indicator (LQI). It is demonstrated that even in a noisy environment, the energy consumption as well as the latency of mobile devices can be significantly reduced.

Gravitational Model of the Three Elements Theory: Mathematical Explanations

The aim is to parse the mathematical details related to the gravitational model of the three elements theory [1]. This model is proven to be coherent and really compatible with relativity. The Riemannian representation of space-time which is used in this model is proven to be legal. It allows to understand relativity in a more human sensitive manner than Minkowskian usual representation.

A verification framework for spatio-temporal consistency language with CCSL as a specification language

The Spatio-Temporal Consistency Language(STeC)is a high-level modeling language that deals natively with spatio-temporal behaviour,i.e.,behaviour relating to certain locations and time.Such restriction by both locations and time is of first importance for some types of real-time systems.CCSL is a formal specification language based on logical clocks.It is used to describe some crucial safety properties for real-time systems,due to its powerful expressiveness of logical and chronometric time constraints.We consider a novel verification framework combining STeC and CCSL,with the advantages of addressing spatio-temporal consistency of system behaviour and easily expressing some crucial time constraints.We propose a theory combining these two languages and a method verifying CCSL properties in STeC models.We adopt UPPAAL as the model checking tool and give a simple example to illustrate how to carry out verification in our framework.

Timed-pNets： a communication behavioural semantic model for distributed systems

This paper presents an approach to build a communication behavioural semantic model for heterogeneous distributed systems that include synchronous and asynchronous communications. Since each node of such system has its own physical clock, it brings the challenges of correctly specifying the system time constraints. Based on the logical clocks proposed by Lamport, and CCSL proposed by Aoste team in INRIA, as well as pNets from Oasis team in INRIA, we develop timed-pNets to model communication behaviours for distributed systems. Timed-pNets are tree style hierarchical structures. Each node is associated with a timed specification which consists of a set of logical clocks and some relations on clocks. The leaves are represented by timed-pLTSs. Non-leaf nodes （called timed-pNets nodes） are synchronisation devices that synchronize the behaviours of subnets （these subnets can be leaves or non-leaf nodes）. Both timed-pLTSs and timed-pNets nodes can be translated to timed specifications. All these notions and methods are illustrated on a simple use-case of car insertion from the area of intelligent transportation systems （ITS）. In the end the TimeSquare tool is used to simulate and check the validity of our model.

Molecular pathways between obesity, non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC)

Obesity represents a major health problem worldwide. World health organization estimated that over 650 million adults were obese in 2016 and 1.9 billion were overweight (1). In the United States, the prevalence of obesity is approximately 36%, whereas it ranges from 10% to 30% in different countries (1-3) in Europe. It is well known that obesity is a strong risk factor for a number of diseases, including diabetes, hyperlipidemia, coronary artery disease, obstructive sleep apnea, chronic kidney disease, depression, and several cancers, such as breast, uterus and colorectal cancer (3).

分布式对象理论：异步-移动-组通信-组件

现今，分布式结构和各种通信对象普遍存在着，在全世界网格和P2P计算环境下，需要完成大量的分布式对象的交互工作，可是，到目前为止还没有一个系统可以对这种交互进行形式化的描述。本书开创性地定义了一种通用性的计算描述形式，利用异步调用的手段来进行分布式对象交互，并且保证其效率和可扩展性。书中介绍的方法还被证明可以解决移动性、组通信以及组件问题。

Scenario-based verification in presence of variability using a synchronous approach

This paper presents a new model of scenarios, dedicated to the specification and verification of system be- haviours in the context of software product lines （SPL）. We draw our inspiration from some techniques that are mostly used in the hardware community, and we show how they could be applied to the verification of software components. We point out the benefits of synchronous languages and mod- els to bridge the gap between both worlds.

Clinical impact of omega-3 fatty acids (Ω3 FA) supplementation on liver surgery

Omega-3 fatty acids(Ω3 FA)are essential nutritional components with beneficial effects on fatty liver and metabolic syndrome affecting blood lipid profiles,membrane lipid composition,eicosanoid biosynthesis,cell signaling cascades,and gene expression(1).They are also involved in a number of metabolic process,including inhibition of several aspects of inflammation,such as leucocyte chemotaxis,adhesion molecule expression and leucocyte-endothelial adhesive interactions,production of eicosanoids like prostaglandins and leukotrienes,production of inflammatory cytokines and T cell reactivity(2).Ω3 FA are particularly abundant in fish and other seafood.