Gastric Cancer: A Stem Cell Disease?

Gastric stem cells have been recently identified and are not yet fully characterized. Each gastric gland or unit is composed of different specialized cells and a small number of discrete stem cells. These gastric stem cells play key roles. They have self-renewal and multipotent properties and are the origin of specialized gastric epithelial cells. These properties are the basis for the stem cells’ role in tissue homeostasis, tissue repair, and cancer. In tumors, growing evidence indicates that a cell subpopulation with stem cell features, the so-called cancer stem cells (CSCs), represents the “fuel” for the tumor: they are at the origin of tumor initiation, growth, and dissemination, and they also display resistance to conventional chemotherapy treatments. The recent identification of CSCs in gastric carcinoma opens the door to the development of new therapeutic strategies targeting more specifically the CSCs at the origin of the disease, which is the third leading cause of cancer-related deaths worldwide

The fate of recessive deleterious or overdominant mutations near mating-type loci under partial selfing

Large regions of suppressed recombination having extended over time occur in many organisms around genes involved in mating compatibility (sex-determining or mating-type genes). The sheltering of deleterious alleles has been proposed to be involved in such expansions. However, the dynamics of deleterious mutations partially linked to genes involved in mating compatibility are not well understood, especially in finite populations. In particular, under what conditions deleterious mutations are likely to be maintained for long enough near mating-compatibility genes remains to be evaluated, especially under selfing, which generally increases the purging rate of deleterious mutations. Using a branching process approximation, we studied the fate of a new deleterious or overdominant mutation in a diploid population, considering a locus carrying two permanently heterozygous mating-type alleles, and a partially linked locus at which the mutation appears. We obtained analytical and numerical results on the probability and purging time of the new mutation. We investigated the impact of recombination between the two loci and of the mating system (outcrossing, intra and inter-tetrad selfing) on the maintenance of the mutation. We found that the presence of a fungal-like mating-type locus (i.e. not preventing diploid selfing) always sheltered the mutation under selfing, i.e. it decreased the purging probability and increased the purging time of the mutations. The sheltering effect was higher in case of automixis (intra-tetrad selfing). This may contribute to explain why evolutionary strata of recombination suppression near the mating-type locus are found mostly in automictic (pseudo-homothallic) fungi. We also showed that rare events of deleterious mutation maintenance during strikingly long evolutionary times could occur, suggesting that deleterious mutations can indeed accumulate near the mating-type locus over evolutionary time scales. In conclusion, our results show that, although selfing purges deleterious mutations, these mutations can be maintained for very long times near a mating-type locus, which may contribute to promote the evolution of recombination suppression in sex-related chromosomes

TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties

Helicobacter pylori infection, the main risk factor for gastric cancer (GC), leads to an epithelial–mesenchymal transition (EMT) of gastric epithelium contributing to gastric cancer stem cell (CSC) emergence. The Hippo pathway e ectors yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) control cancer initiation and progression in many cancers including GC. Here, we investigated the role of TAZ in the early steps of H. pylori-mediated gastric carcinogenesis. TAZ implication in EMT, invasion, and CSC-related tumorigenic properties were evaluated in three gastric epithelial cell lines infected by H. pylori. We showed that H. pylori infection increased TAZ nuclear expression and transcriptional enhancer TEA domain (TEAD) transcription factors transcriptional activity. Nuclear TAZ and zinc finger E-box-binding homeobox 1 (ZEB1) were co-overexpressed in cells harboring a mesenchymal phenotype in vitro, and in areas of regenerative hyperplasia in gastric mucosa of H. pylori-infected patients and experimentally infected mice, as well as at the invasive front of gastric carcinoma. TAZsilencing reduced ZEB1 expression andEMTphenotype, and strongly inhibited invasion and tumorsphere formation induced by H. pylori. In conclusion, TAZ activation in response to H. pylori infection contributes to H. pylori-induced EMT, invasion, and CSC-like tumorigenic properties. TAZ overexpression in H. pylori-induced pre-neoplastic lesions and in GC could therefore constitute a biomarker of early transformation in gastric carcinogenesis.Ligue Nationale Française Contre le Cancer (French National League against Cancer)/[]//FranciaUniversidad de Costa Rica/[]/UCR/Costa RicaMinisterio de Ciencia, Innovación, Tecnología y Telecomunicaciones/[]/MICITT/Costa RicaFrench National Cancer Institute/[PLBio 2014-152]/INCa/FranciaLigue Contre le Cancer/[]//FranciaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

The Hippo Kinase LATS2 Controls Helicobacter pylori-Induced Epithelial-Mesenchymal Transition and Intestinal Metaplasia in Gastric Mucosa

Gastric carcinoma is related mostly to CagA+-Helicobacter pylori infection, which disrupts the gastric mucosa turnover and elicits an epithelial-mesenchymal transition (EMT) and preneoplastic transdifferentiation. The tumor suppressor Hippo pathway controls stem cell homeostasis; its core, constituted by the large tumor suppressor 2 (LATS2) kinase and its substrate Yes-associated protein 1 (YAP1), was investigated in this context.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

MRI-Based Radiomics Input for Prediction of 2-Year Disease Recurrence in Anal Squamous Cell Carcinoma

International audiencePurpose: Chemo-radiotherapy (CRT) is the standard treatment for non-metastatic anal squamous cell carcinomas (ASCC). Despite excellent results for T1-2 stages, relapses still occur in around 35% of locally advanced tumors. Recent strategies focus on treatment intensification, but could benefit from a better patient selection. Our goal was to assess the prognostic value of pre-therapeutic MRI radiomics on 2-year disease control (DC). Methods: We retrospectively selected patients with non-metastatic ASCC treated at the CHU Bordeaux and in the French FFCD0904 multicentric trial. Radiomic features were extracted from T2-weighted pre-therapeutic MRI delineated sequences. After random division between training and testing sets on a 2:1 ratio, univariate and multivariate analysis were performed on the training cohort to select optimal features. The correlation with 2-year DC was assessed using logistic regression models, with AUC and accuracy as performance gauges, and the prediction of disease-free survival using Cox regression and Kaplan-Meier analysis. Results: A total of 82 patients were randomized in the training (n = 54) and testing sets (n = 28). At 2 years, 24 patients (29%) presented relapse. In the training set, two clinical (tumor size and CRT length) and two radiomic features (FirstOrder_Entropy and GLCM_JointEnergy) were associated with disease control in univariate analysis and included in the model. The clinical model was outperformed by the mixed (clinical and radiomic) model in both the training (AUC 0.758 versus 0.825, accuracy of 75.9% versus 87%) and testing (AUC 0.714 versus 0.898, accuracy of 78.6% versus 85.7%) sets, which led to distinctive high and low risk of disease relapse groups (HR 8.60, p = 0.005). Conclusion: A mixed model with two clinical and two radiomic features was predictive of 2-year disease control after CRT and could contribute to identify high risk patients amenable to treatment intensification with view of personalized medicine

Principes, enjeux et usages de la méthode biographique en sociologie

This paper shows that the practice of a biographical method in sociology is a tool particularly useful for this branch of knowledge when the researcher focuses on socialization processes. The biographical method enables analyzing the genesis of social phenomena, through the deep analysis of the dispositions of an individual. It allows grasping social reality in an individual way. The conditions enabling this approach, inspired by Jean Peneff, are considered, together with some examples of its use.Nous défendons dans cet article l'usage de la méthode biographique comme un outil particulièrement opérant dans le cadre d'une démarche sociologique plaçant au centre de sa réflexion les processus de socialisation. La méthode biographique permet de penser la genèse des phénomènes sociaux, à travers la reconstruction fine et précise des dispositions d'un individu, et ainsi de saisir le social sous sa forme individuelle. Après avoir défini le statut épistémologique de cette méthode biographique, inspirée de Jean Peneff, nous réfléchissons à ses conditions pratiques de possibilité et en présentons des usages

RNA Extraction from Ears and Draining Lymph Nodes of Mice Infected with Leishmania amazonensis

International audienceParasites of the genus Leishmania infect the mammalian hosts, including mice and humans and cause cutaneous or visceral leishm aniasis depending upon the parasite species transmitted by the vector sandfly. Leishmania amazonensis is one of the Leishmania species responsible for th e cutaneous form of the disease. We have inoculated with these parasites the ear dermis of mice. RNA preparations were performed from fragmented tissues using a buffer containing guanidin isothiocynate (RLT buffer, RNeasy Mini Kit, Qiagen, SAS, France) and β mercaptoethanol. Both reagents facilitate the isolation of intact RNA from tissues and the use of the RNeasy Kits present with several advantages that facilitate the isolation of pure non degraded total RNA: i) T his method allows to avoid the presence o f phenol in the RNA extraction buffer, commonly used in alternative protocols; ii) Moreover Diethylpyrocarbonate (DEPC) treatment of glassware, to avoid RNAses contamination of the samples, is not required with this protocol; iii) F inally, it is a fast pro cedure and the isolated total RNA may be concentrated in a small volume thus facilitating its use for downstream experimental procedures

Des vies à l'œuvre : agencements pluriels de socialisations

International audienc