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

Multifaceted oncogenic role of adipocytes in the tumour microenvironment

Obesity has for decades been recognised as one of the major health concerns. Recently accumulated evidence has established that obesity or being overweight is strongly linked to an increased risk of cancer. However, it is still not completely clear how adipose tissue (fat), along with other stromal connective tissues and cells, contribute to tumour initiation and progression. In the tumour microenvironment, the adipose tissue cells, in particular the adipocytes, secrete a number of adipokines, including growth factors, hormones, collagens, fatty acids, and other metabolites as well as extracellular vesicles to shape and condition the tumour and its microenvironment. In fact, the adipocytes, through releasing these factors and materials, can directly and indirectly facilitate cancer cell proliferation, apoptosis, metabolism, angiogenesis, metastasis and even chemotherapy resistance. In this chapter, the multidimensional role played by adipocytes, a major and functional component of the adipose tissue, in promoting cancer development and progression within the tumour microenvironment will be discussed

Adipose Tissue Increase Dramatically the Tumour Growth When Co-Injected with Breast Cancer Cell Lines: A Prudence Recommendation for Autologous Fat Transfer in Breast.

Abstract Background: Autologous fat transfer takes an increasingly importance in plastic surgery. Indeed during the last decade, fat transfer was first of all used for breast reconstruction and now in breast augmentation, breast asymmetry, breast defects after lumpectomy and in some other breast deformation. Nevertheless this extension of the technique in the mammary parenchyma raises several questions. One of the most crucial interrogation is related to the type of interaction induced by the adipose tissue grafted with the breast cancer cells, interaction which remains poorly understood. Data from the literature evoked that these interactions lead to induce the increase of tumour growth properties. To decipher this interrogation, we designed experiments whose aims are to better understand and evaluate the actions and interactions induced by the xenograft of adipose tissue plus breast cancer cells in terms of tumour growth properties.Method: To study the impact of fat in tumours growth properties, we performed experiments of co-implantation of a panel of breast cancer cell lines (two humans: MDAMB-231 and SUM-159 PT ; and one mice: 67NR) with human adipose tissue from abdominal liposuction in nude mice. It was reported that tumour progression is the product of an evolving cross talk between tumour cells and its surrounding supportive tissue, the tumour stroma. Since mature adipocytes are radioresistant compared to other components of the tumour stroma, we investigated the effect of irradiated (15 Gray) or not adipose tissue on tumour growth properties. In each experiment we used 3 groups. The first one xenografted with cell lines only, the second one xenografted with cell plus fat and in the last constituted of cell plus irradiated fat. At the end of experiments mice were sacrificed and tumours were removed, dissected and one part was fixed and the other one (piece 2mm3) was re-implanted in a new mice. In these new groups we also studied the tumours growth and tumours tissue as previously described to evaluate the “possible” long time effect.Results-discussion: We have showed, whatever the cell line, that co-implantation of human fat (irradiated or not) with breast cancer cell lines induces a dramatic increase in tumour growth properties compared to cell line alone. Furthermore, the preliminary in vitro results associated to the ongoing immunohistochemistry analysis performed in the tumours from in vivo experiments of co-injection of fat plus breast cancer cell lines, gives related-results in term of tumour growth properties such as those observed in the in vivo experiment. Even-if larger in vitro studies are needed and are ongoing to consolidate our in vivo results, the whole of these results lead us to emit a recommendation of prudence with respect to this technique in mammary parenchyma. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3102.</jats:p

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