A microRNA Signature Associated with Early Recurrence in Breast Cancer.

Recurrent breast cancer occurring after the initial treatment is associated with poor outcome. A bimodal relapse pattern after surgery for primary tumor has been described with peaks of early and late recurrence occurring at about 2 and 5 years, respectively. Although several clinical and pathological features have been used to discriminate between low- and high-risk patients, the identification of molecular biomarkers with prognostic value remains an unmet need in the current management of breast cancer. Using microarray-based technology, we have performed a microRNA expression analysis in 71 primary breast tumors from patients that either remained disease-free at 5 years post-surgery (group A) or developed early (group B) or late (group C) recurrence. Unsupervised hierarchical clustering of microRNA expression data segregated tumors in two groups, mainly corresponding to patients with early recurrence and those with no recurrence. Microarray data analysis and RT-qPCR validation led to the identification of a set of 5 microRNAs (the 5-miRNA signature) differentially expressed between these two groups: miR-149, miR-10a, miR-20b, miR-30a-3p and miR-342-5p. All five microRNAs were down-regulated in tumors from patients with early recurrence. We show here that the 5-miRNA signature defines a high-risk group of patients with shorter relapse-free survival and has predictive value to discriminate non-relapsing versus early-relapsing patients (AUC = 0.993, p-value<0.05). Network analysis based on miRNA-target interactions curated by public databases suggests that down-regulation of the 5-miRNA signature in the subset of early-relapsing tumors would result in an overall increased proliferative and angiogenic capacity. In summary, we have identified a set of recurrence-related microRNAs with potential prognostic value to identify patients who will likely develop metastasis early after primary breast surgery.

A neuron-specific deletion of the microRNA-processing enzyme DICER induces severe but transient obesity in mice.

MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression post-transcriptionally. MiRNAs are implicated in various biological processes associated with obesity, including adipocyte differentiation and lipid metabolism. We used a neuronal-specific inhibition of miRNA maturation in adult mice to study the consequences of miRNA loss on obesity development. Camk2a-CreERT2 (Cre+) and floxed Dicer (Dicerlox/lox) mice were crossed to generate tamoxifen-inducible conditional Dicer knockouts (cKO). Vehicle- and/or tamoxifen-injected Cre+;Dicerlox/lox and Cre+;Dicer+/+ served as controls. Four cohorts were used to a) measure body composition, b) follow food intake and body weight dynamics, c) evaluate basal metabolism and effects of food deprivation, and d) assess the brain transcriptome consequences of miRNA loss. cKO mice developed severe obesity and gained 18 g extra weight over the 5 weeks following tamoxifen injection, mainly due to increased fat mass. This phenotype was highly reproducible and observed in all 38 cKO mice recorded and in none of the controls, excluding possible effects of tamoxifen or the non-induced transgene. Development of obesity was concomitant with hyperphagia, increased food efficiency, and decreased activity. Surprisingly, after reaching maximum body weight, obese cKO mice spontaneously started losing weight as rapidly as it was gained. Weight loss was accompanied by lowered O2-consumption and respiratory-exchange ratio. Brain transcriptome analyses in obese mice identified several obesity-related pathways (e.g. leptin, somatostatin, and nemo-like kinase signaling), as well as genes involved in feeding and appetite (e.g. Pmch, Neurotensin) and in metabolism (e.g. Bmp4, Bmp7, Ptger1, Cox7a1). A gene cluster with anti-correlated expression in the cerebral cortex of post-obese compared to obese mice was enriched for synaptic plasticity pathways. While other studies have identified a role for miRNAs in obesity, we here present a unique model that allows for the study of processes involved in reversing obesity. Moreover, our study identified the cortex as a brain area important for body weight homeostasis.

Catalogue des livres portraits, gravures & instruments d'optique. Composant la Bibliothèque et le Cabinet De feu M. Grangeret de Lagrange conservateur-adjoint à la bibliothèque de l'Arsenal, membre du conseil de la Société asiatique, ancien correcteur pour les livres orientaux à l'Imprimerie impériale, etc. : La vente aura lieu ... Les Mardi 19, Mercredi 20, Jeudi 21 et Vendredi 22 Juillet 1859 / [expert] M. Auguste Aubry, Libraire

[Vente. Livres. 1859-07-19 - 1859-07-22]

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.

A dramatic lung cancer course in a patient with a rare EGFR germline mutation exon 21 V843I: Is EGFR TKI resistance predictable?

We report on the medical history of a Caucasian smoker woman diagnosed with a stage IV NSCLC adenocarcinoma, characterized by a rare epidermal growth factor receptor (EGFR) point mutation in exon 21 codon 843 (p.V843I/c.2527G>A/COSMIC ID 85894). This genetic alteration revealed to be germline, after its presence was demonstrated in chondroblasts from the bone biopsy. While it is the first description of germline V843I mutation without concomitant additional known EGFR activating mutation, we modeled the EGFR ATP catalytic domain in complex with ATP, gefitinib and erlotinib using computer-aided approaches to estimate possible changes in affinity upon the V843I mutation.

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Das Management von öffentlichen Organisationen hat sich in den letzen drei, vier Jahrzehnten beachtlich weiterentwickelt. Stichworte sind: verstärkte Ergebnisorientierung, grössere Autonomie bezüglich der Nützung der Ressourcen und der Prioritätensetzung, gesteigerte Ansprüche hinsichtlich der Rechenschaftslegung (Accountability), das gestiegene Interesse der Bürger und Medien an Entscheidungen und Tätigkeiten der öffentlichen Hand usw. Managementmethoden, die teils aus der Privatwirtschaft stammen, teils jedoch speziell für den öffentlichen Sektor entwickelt wurden, vervollständigen die Palette an Instrumenten, die den Public Managern heute zur Verfügung stehen. Dabei spielt die Kommunikation eine wichtige Rolle - sowohl innerhalb der Organisationen selbst wie Auch gegenüber der Gesamtheit ihrer Anspruchsgruppen und der Gesellschaft als Ganzes. Von den Verantwortlichen der öffentlichen Hand wird zunehmend erwartet, dass sie die Probleme und Herausforderungen der Politik offen darlegen, getroffene Entscheidungen erklären, die dazu benötigten Mittel rechtfertigen und die Bedürfnisse und Anforderungen der Leistungsempfänger berücksichtigen.

Cannes 21-1-20, Miss Ryan [Elisabeth] et Ritchie [Josiah] [contre] Mlle Lenglen [Suzanne] et Albarran [Pierre] [tournoi de lawn-tennis du Carlton-Club de Cannes] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57735

Lottery Action, July 8-21, 2002, Vol. 9 no. 13

Iowa Lottery Authority Retailer Information Newsletter

Lottery Action, October 21-November 3, 2002, Vol. 9, no. 20

Newsletter for Iowa Lottery

Lottery Action, November 4-17, 2002, Vol. 9, no. 21

Newsletter for Iowa Lottery

Lottery Action, September 8-21, 2003, Vol. 10, no. 18

Newsletter for Iowa Lottery

Cannes, 21-1-20, prince Philippe de Bourbon [jouant au tennis] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57740

Cannes 21-1-20, lord Rochsavage [i. e. marquis de Cholmondeley au tournoi de lawn-tennis du Carlton-Club de Cannes] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57737