Effects of Dietary Restriction on Cancer Development and Progression

The effects of caloric restriction on tumor growth and progression are known for over a century. Indeed, fasting has been practiced for millennia, but just recently has emerged the protective role that it may exert toward cells. Fasting cycles are able to reprogram the cellular metabolism, by inducing protection against oxidative stress and prolonging cellular longevity. The reduction of calorie intake as well as short- or long-term fasting has been shown to protect against chronic and degenerative diseases, such as diabetes, cardiovascular pathologies, and cancer. In vitro and in vivo preclinical models showed that different restriction dietary regimens may be effective against cancer onset and progression, by enhancing therapy response and reducing its toxic side effects. Fasting-mediated beneficial effects seem to be due to the reduction of inflammatory response and downregulation of nutrient-related signaling pathways able to modulate cell proliferation and apoptosis. In this chapter, we will discuss the most significant studies present in literature regarding the molecular mechanisms by which dietary restriction may contribute to prevent cancer onset, reduce its progression, and positively affect the response to the treatments

ASTRID Nuclear Island design : advances in French-Japanese joint team development of Decay Heat Removal systems

International audienceASTRID (Advanced Sodium Technological Reactor for Industrial Demonstration) has the objective to integrate innovative options with the objective to prepare the 4th generation reactors.In this framework a French-Japanese agreement was signed in 2014 between CEA, AREVA NP, JAEA, MHI/MFBR to jointly perform components design of ASTRID such as Decay Heat Removal Systems (DHRS).In this respect an ambitious close collaboration is set in the framework of the practical elimination objective of Decay Heat Removal function loss which is one of the main ASTRID safety objectives.To reach this target, design is driven by deterministic safety criteria, probabilistic safety indicators and proper technical and economic analysis.Safety demonstration aims at identifying common cause failures and imposes to search for proper diversification of decay heat removal systems. In ASTRID, DHRS diversification is based on final heat sinks types, intermediate coolant fluids and spatial segregation of systems with different thermal loading during normal operation as well as severe accident exposure. Implication of two different designers bodies AREVA NP and a Japanese team (JAEA, Mitsubishi FBR Systems (MFBR) and MHI) also participate to diversification.This paper is giving highlights of ASTRID DHRS current strategy. Focus is made on operating temperature diversification for in-vessel heat exchanger as well as core catcher coolability by an original features such as heat exchanger located within reactor cold pool, whose design was taken over by Japan team since 2014

Progress in the ASTRID Gas Power Conversion System development

International audienceWithin the framework of the French 600 MWe Advanced Sodium Technological Reactor for Industrial Demonstration project (ASTRID), two options of Power Conversion System (PCS) were studied during the conceptual design phase (2010-2015)- the use of a classical Rankine water-steam cycle, similar to the solution implemented in France in Phenix and Superphenix, but with the goal of greatly reducing the probability of occurrence and limiting the potential consequences of a sodium-water reaction; chosen as the reference for the ASTRID Plant Model during the conceptual design phase due its high level of maturity,- an alternative approach using a Brayton gas cycle which has never been implemented in any Sodium Fast Reactor. Its application is mainly justified by safety and acceptance considerations in inherently eliminating the sodium-water and sodium-water-air reaction risk existing with a Rankine cycle.The ASTRID conceptual design phase period allowed to greatly increase the maturity level of a standalone Gas Power Conversion System option. Thus, it has been decided to lay during the 2016-2017 phase the ASTRID Gas PCS integration studies at the same level as that achieved by the ASTRID water-steam based PCS at the end of 2015. The 2016-2017 period, in which the Gas PCS is integrated in the overall layout of the reactor, will allow to better specify the technical and economic implications of the selection of the Gas PCS taking into account all the aspects of the integration of such an option. A well-documented comparison between the two systems will be therefore facilitated.This paper resumes progress in the integration of the Gas Power Conversion System in the Astrid Reactor Plant Model. It describes the characteristics of main systems particularly the turbomachinery, the Heat Exchangers (Sodium/Gas, Gas/Gas and Gas/Water) and the Gas Inventory Management System

The role of the physiatrist in the haemophilia comprehensive care team in different parts of the world

The role of the physiatrist, as a member of the multidisciplinary haemophilia comprehensive care team, is to prevent and treat activity limitations and restriction of participation on the part of the patient. . This role is threefold: (i) provide education to the patients, families and healthcare providers to detect disabling injuries and take adequate precautions; (ii) provide specialized treatment of musculoskeletal disabilities striving for the highest level of functionality and (iii) Stimulate the patient's full participation in socio-economic activities of his country. Prominent physiatrists from different parts of the world describe the situation in Armenia, China, Egypt, France, Indonesia (and the Philippines), the Netherlands and South America

Dosimétrie chez le lapin d'[131I]ICF01012 en vue de son utilisation pour le traitement du mélanome métastatique par radiothérapie interne vectorisée

National audienc

Inhibition of the GTPase Rac1 Mediates the Antimigratory Effects of Metformin in Prostate Cancer Cells

International audienceCell migration is a critical step in the progression of prostate cancer to the metastatic state, the lethal form of the disease. The antidiabetic drug metformin has been shown to display antitumoral properties in prostate cancer cell and animal models; however, its role in the formation of metastases remains poorly documented. Here, we show that metformin reduces the formation of metastases to fewer solid organs in an orthotopic metastatic prostate cancer cell model established in nude mice. As predicted, metformin hampers cell motility in PC3 and DU145 prostate cancer cells and triggers a radical reorganization of the cell cytoskeleton. The small GTPase Rac1 is a master regulator of cytoskeleton organization and cell migration. We report that metformin leads to a major inhibition of Rac1 GTPase activity by interfering with some of its multiple upstream signaling pathways, namely P-Rex1 (a Guanine nucleotide exchange factor and activator of Rac1), cAMP, and CXCL12/CXCR4, resulting in decreased migration of prostate cancer cells. Importantly, overexpression of a constitutively active form of Rac1, or P-Rex, as well as the inhibition of the adenylate cyclase, was able to reverse the antimigratory effects of metformin. These results establish a novel mechanism of action for metformin and highlight its potential antimetastatic properties in prostate cancer