HLA-G is a nonclassical class I molecule that differs from classical antigens by its restricted expression, very low polymorphism, expression of 7 different protein isoforms, and immune tolerance-inducing activity. HLA-G plays a key role in feto-maternal tolerance. Its interaction with three specific receptors expressed on immune cells (T, B, natural killer and antigen-presenting cells) allows it to act at all levels of the immune response. HLA-G can also be expressed by tumor cells and their microenvironment, endowing them with significant local tolerance. The same is true in some inflammatory and viral diseases.

Retinoblastoma is a malignant tumor arising from retinal stem cells or retinoblasts. Its management has been well determined. The goal of this study is to report preliminary results obtained with combined chemotherapy and surgical treatment.

Pulmonary blastoma, a rare primary lung malignancy is subdivided in 3 categories: well-differentiated fetal adenocarcinoma (WDFA), classic biphasic pulmonary blastoma (CBPB) and pleuropulmonary blastoma (PPB). Classic pulmonary blastoma is composed of a mixture of immature epithelial and mesenchymal tissue resembling fetal lung tissue.

The current theory, known as the "theory ofenergy balance", perceives paediatric obesity, like adults' obesity, as the result of an excessively positive energy balance. Thus, prevention endeavours have focused on controlling calories intake and dietary education, with increases in physical activity (PA) having just a supporting role. Paradoxically, preventive programmes developed with this vision are not satisfactory, whereas some recent findings suggest, that in the growing body of youths, PA may stimulate stem cells to differentiate preferentially into lean tissue. These observations advocate the emergence of a new theoretical framework to childhood obesity prevention: the "developmental theory", which posits the pre-eminence of PA. As a result, preventive strategies that would emphasise vigorous PA rather than food intake control can help youths develop lean bodies, at the same time that they ingest sufficient amounts of the energy and accompanying nutrients needed for a healthy growth.

2013 has been the year of publications of large multicentric studies defining the modalities of different anti-VEGF and corticoid implants for the treatment of retinal diseases. The real innovation has been the growing use of iPS cells in the field of ophthalmology opening new hopes for the treatment of incurable blinding diseases.

During two centuries, advances in medicine and medical research have helped to understand the pathophysiology of chronic myelogenous leukemia (CML). This hematologic malignancy is a unique model of oncogenesis where a single molecular hit, causing cell proliferation and survival, was identified. The chromosomal abnormality first highlighted by P. Nowell and D. Hungerford in 1960, and characterized as the reciprocal translocation t(9;22)(q34;q11), the Philadelphia chromosome, discovered in leukemic cells, by J. Rowley in 1973. At the end of the 20th century, the contribution of molecular biology techniques was crucial by the discovery of the BCR-ABL1 hybrid oncogene derived from the t(9;22), responsible for the translation of an aberrant protein tyrosine kinase. This BCR-ABL1 kinase deregulates signaling pathways that control normal cell cycle and survival in primitive hematopoietic cells and is thus responsible for malignant cell accumulation observed in CML. It was then only necessary to develop a targeted treatment adapted to this molecular hit. Recently, tyrosine kinase inhibitors, by their specific inhibitory activity of BCR-ABL, have revolutionized the treatment of CML, allowing rates of haematological, cytogenetic and molecular responses never seen to date, and has significantly improved the overall survival and the quality of life of patients.

Stem cells are required for both tissue renewal and repair in response to injury. The maintenance and function of stem cells is controlled by their specific cellular microenvironment called "niche". Hematopoietic stem cells (HSC) that give rise to all blood cell types have been extensively studied in mammals. Genetic and molecular analyses performed in mice identified several signaling pathways involved in the cellular communications between HSC and their niche. However, hematopoietic niche plasticity remains poorly understood. The discovery of a Drosophila hematopoietic niche, called PSC, established a new model to decipher the niche function in vivo. Size control of the PSC is essential to maintain hematopoietic tissue homeostasis and a molecular cascade controlling the PSC cell number has been characterized. Novel parallels between Drosophila and mammalian hematopoietic niches open new perspectives for studies of HSC biology in human.

Tooth extraction as a part of dental care provides an opportunity to obtain dental pulp stem cells that could constitute new therapeutic tools for craniofacial bone and teeth repair. However, the use of tooth as a biological sample of human origin must comply with legislation and ethical rules.

The detection and molecular characterization of circulating tumor cells (CTCs) are one of the most active areas of translational cancer research, with more than 400 clinical studies having included CTCs as a biomarker. The aims of research on CTCs include: a) estimation of the risk for metastatic relapse or metastatic progression (prognostic information); b) stratification and real-time monitoring of therapies; c) identification of therapeutic targets and resistance mechanisms; and d) understanding metastasis development in cancer patients. This review focuses on the technologies used for the enrichment and detection of CTCs. We outline and discuss the current technologies that are based on exploiting the physical and biological properties of CTCs. A number of innovative technologies to improve methods for CTC detection have recently been developed, including CTC microchips, filtration devices, quantitative reverse-transcription PCR assays, and automated microscopy systems. Molecular characterization studies have indicated, however, that CTCs are very heterogeneous, a finding that underscores the need for multiplex approaches to capture all of the relevant CTC subsets. We therefore emphasize the current challenges of increasing the yield and detection of CTCs that have undergone an epithelial-mesenchymal transition. Increasing assay analytical sensitivity may lead, however, to a decrease in analytical specificity (e.g., through the detection of circulating normal epithelial cells). A considerable number of promising CTC detection techniques have been developed in recent years. The analytical specificity and clinical utility of these methods must be demonstrated in large prospective multicenter studies to reach the high level of evidence required for their introduction into clinical practice.

Despite therapeutic advances, heart failure remains a common and serious event characterized by initial and progressive loss of cardiac myocytes, a loss that is currently untreatable. Cell therapy has emerged as a promising new approach to the treatment of heart failure, with very encouraging experimental results. Since 2000, when human stem cell therapy was first attempted in France, clinical trials with adult stem cells (myoblasts, bone-marrow derived cells, mesenchymal stem cells) have given variable results. The inconsistent and modest therapeutic benefit observed in these studies is due more to paracrine effects than to the hoped-for cell replacement, as adult stem cells do not turn into cardiomyocytes and their survival rate after transplantation is very low. In order to be effective, cell therapy should use heart muscle cells derived from pluri- or multipotent cells (human embryonic stem cells, induced pluripotent stem cells, resident cardiac cells), which are likely to have a higher survival rate in a hostile biological environment and deteriorated tissue scaffold. Cardiac tissue engineering assisted by nanotechnologies may eventually help to meet this challenge.

Mesenchymal stromal cells (MSC) are multipotent and self-renewing cells. MSC are studied for their in vivo and in vitro immunomodulatory effects, in the prevention or the treatment of isehemic injury, and for their potential properties of tissue or organ reconstruction. Over the last few years, the potential role of MSC in organ transplantation has been studied both in vitro and in vivo, and their properties make them an ideal potential cell therapy after solid organ transplantation. A prospective, controlled, phase 1-2 study has been initiated at the CHU of Liege, Belgium. This study assesses the potential risks and benefits of MSC infusion after liver or kidney transplantation. Even if the preliminary results of this study look promising, solely a prospective, randomized, large scale, phase 3 study will allow the clinical confirmation of the theoretical benefits of MSC in solid organ transplantation.

In aged human, the number of muscle fibers and motor units decreases. The remaining motor units lose their functionality (decrease of the discharge frequency, greater fluctuation of the discharge) particularly those which contain type II fibers. The renewal of intracellular proteins declines which creates a negative balance between the daily protein losses and the capacities to renew them. The activity of the protein kinase (Akt) that stimulates the synthesis of regulation proteins (mTOR, p70S6, IGFBP-5) declines whereas the factors of degradation of proteins (NF-kappa B) are activated. Besides, the process of activation and proliferation of satellite cells is affected and the production of anabolic hormones and local factors is decreased. After a strength training program, muscle hypertrophy is linked to the protein synthesis at the level of myosin heavy chain (MHC) isoforms in older subjects. However, the transcription of the genes that code the MHC-I (slow form) increases and the transcription of the genes that code the MHC-II (fast form) decreases. Thus, the transition of the phenotype towards a slower form cannot be inverted by strength training during the advanced in age. Moreover, strength training enables to decrease the proportion of fibers containing MHC of hybrid form in the process of evolution. Hence, strength training can engender a stabilization of the muscular phenotype i.e. different isoforms of MHC. In addition, strength training counteracts the noxious effects mentioned above by generating muscular hypertrophy thanks to a reactive increase in the production of anabolic hormones. A program of aerobic training can induce an increase in the synthesis of ARN messengers coding isoforms related to the oxidative metabolism (MHC-I and to a lesser extent MHC-IIa) while the transcribed for the type MHC-IIx decrease.

Cutaneous melanoma is a malignant tumor with a high metastatic potential. If an early treatment is associated with a favorable outcome, the prognosis of metastatic melanoma remains poor. Advances in molecular characterization of cancers, notably the discovery of BRAF gene mutations in metastatic melanoma, allowed to the recent development of targeted therapies against mutated BRAF protein. Despite high tumor response rates observed in clinical trials, these new drugs are associated with frequent secondary tumor resistance occurrence and paradoxical carcinogenic side effects. The cellular and molecular mechanisms of these carcinogenic side effects and secondary resistance are not yet fully elucidated and are actually intensely studied. This review of the literature focus on the mechanisms of these carcinogenic side effects and on the tumor resistance associated with anti-BRAF targeted therapies.

Pluripotency is a transitory state during vertebrate development. A pluripotent cell can theoretically acquire all cell fates of the organism. During ontogenetic dynamics, loss of pluripotency is associated with a progressive acquisition of a specific genetic program, which is determined both by instructions received and by cell position in the whole organism. Pluripotent embryonic stem cells can be isolated and cultured in vitro indefinitely. Using mammalian embryonic stem cells (ESCs), it has been possible to identify the factors involved in the establishment and maintenance of pluripotency state. In this review, we will describe recent scientific advances in the understanding of pluripotency, the molecular actors involved in such a regulation and their functional conservation during evolution. We shall focus on new concepts, obtained from the study of vertebrate model organisms, to shed light on the cell transition from pluripotency to differentiated state, and shall recapitulate fundamental and clinical applications of pluripotent cells, of "somatic cell nuclear transfer" (SCNT), of induced nuclear reprogramming in vitro and future perspectives of in vivo applications. Our results, in the xenopus, concerning the first in vivo induced nuclear reprogramming might open new perspectives about the understanding of cell plasticity in an integrated context. Our analyses sought to encourage new and alternative clinical approaches to achieve in situ tissue regeneration.