MicroRNA-200 family modulation in distinct breast cancer phenotypes.

The epithelial to mesenchymal transition (EMT) contributes to tumor invasion and metastasis in a variety of cancer types. In human breast cancer, gene expression studies have determined that basal-B/claudin-low and metaplastic cancers exhibit EMT-related characteristics, but the molecular mechanisms underlying this observation are unknown. As the family of miR-200 microRNAs has been shown to regulate EMT in normal tissues and cancer, here we evaluated whether the expression of the miR-200 family (miR-200f) and their epigenetic state correlate with EMT features in human breast carcinomas. We analyzed by qRT-PCR the expression of miR-200f members and various EMT-transcriptional inducers in a series of 70 breast cancers comprising an array of phenotypic subtypes: estrogen receptor positive (ER+), HER2 positive (HER2+), and triple negative (TN), including a subset of metaplastic breast carcinomas (MBCs) with sarcomatous (homologous or heterologous) differentiation. No MBCs with squamous differentiation were included. The DNA methylation status of miR-200f loci in tumor samples were inspected using Sequenom MassArray® MALDI-TOF platform. We also used two non-tumorigenic breast basal cell lines that spontaneously undergo EMT to study the modulation of miR-200f expression during EMT in vitro. We demonstrate that miR-200f is strongly decreased in MBCs compared with other cancer types. TN and HER2+ breast cancers also exhibited lower miR-200f expression than ER+ tumors. Significantly, the decreased miR-200f expression found in MBCs is accompanied by an increase in the expression levels of EMT-transcriptional inducers, and hypermethylation of the miR-200c-141 locus. Similar to tumor samples, we demonstrated that downregulation of miR-200f and hypermethylation of the miR-200c-141 locus, together with upregulation of EMT-transcriptional inducers also occur in an in vitro cellular model of spontaneous EMT. Thus, the expression and methylation status of miR-200f could be used as hypothetical biomarkers to assess the occurrence of EMT in breast cancer.

Biblia sacra, pars. III

Evangeliorum canones (4v) ; Evang. Matthaei (13v), Marci (33v), Lucae (47v), Johannis (68v) ; XIV Epist. Pauli (88) ; Actus Apost. (139v) ; VII Epist. canon. (161) ; Apocalypsis (172v).

Rab18 dynamics in adipocytes in relation to lipogenesis, lipolysis and obesity.

Lipid droplets (LDs) are organelles that coordinate lipid storage and mobilization, both processes being especially important in cells specialized in managing fat, the adipocytes. Proteomic analyses of LDs have consistently identified the small GTPase Rab18 as a component of the LD coat. However, the specific contribution of Rab18 to adipocyte function remains to be elucidated. Herein, we have analyzed Rab18 expression, intracellular localization and function in relation to the metabolic status of adipocytes. We show that Rab18 production increases during adipogenic differentiation of 3T3-L1 cells. In addition, our data show that insulin induces, via phosphatidylinositol 3-kinase (PI3K), the recruitment of Rab18 to the surface of LDs. Furthermore, Rab18 overexpression increased basal lipogenesis and Rab18 silencing impaired the lipogenic response to insulin, thereby suggesting that this GTPase promotes fat accumulation in adipocytes. On the other hand, studies of the β-adrenergic receptor agonist isoproterenol confirmed and extended previous evidence for the participation of Rab18 in lipolysis. Together, our data support the view that Rab18 is a common mediator of lipolysis and lipogenesis and suggests that the endoplasmic reticulum (ER) is the link that enables Rab18 action on these two processes. Finally, we describe, for the first time, the presence of Rab18 in human adipose tissue, wherein the expression of this GTPase exhibits sex- and depot-specific differences and is correlated to obesity. Taken together, these findings indicate that Rab18 is involved in insulin-mediated lipogenesis, as well as in β-adrenergic-induced lipolysis, likely facilitating interaction of LDs with ER membranes and the exchange of lipids between these compartments. A role for Rab18 in the regulation of adipocyte biology under both normal and pathological conditions is proposed.

ordo Romanae Ecclesiae curiaeque, qui obtinuit à temporibus Innocentii Papae III. ad Clementem V.

Colbertinus

Prevalence and Clinical Outcomes for Patients With ALK-Positive Resected Stage I to III Adenocarcinoma: Results From the European Thoracic Oncology Platform Lungscape Project.

PURPOSE: The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non-small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population. METHODS: Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for FISH testing. Testing was performed in 16 participating centers, using the same protocol after passing external quality assessment. RESULTS: Positive ALK IHC staining was present in 80 patients (prevalence of 6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to 46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+ patients. The hazard of death for FISH-positive patients was lower than for IHC-negative patients (P = .022). Multivariable models, adjusted for patient, tumor, and treatment characteristics, and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better overall survival (OS). CONCLUSION: In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening strategy based on IHC or H-score could be envisaged. ALK positivity (by either IHC or FISH) was related to better OS.

Control d'un robot de 3 graus de llibertat

Partint d'una estructura robòtica de 3 graus de llibertat, s'ha de fer el disseny deles unitats de potència i control , muntatge, conexionat, programació i posta enmarxa per poder generar trajectòries des d'un PC.Per aconseguir l'objectiu s'han realitzat les següents fites:a) Ajust i modificacions mecàniques de la estructura robòticaSubstitució de xavetes i canvi de pinyons.b) Implementar, modificar i ajustar elements elèctrics del robot.Substitució de motor elèctric espatllat, realitzar un nou cablejat cap a lanova unitat de control i substitució d'un sensor de posició.c) Disseny i muntatge de la unitat de potènciaSelecció de la targeta MD03 per controlar l'alimentació, velocitat i sentitde gir del motors, que controlen els 3 graus de llibertat. Mecanització enuna caixa incloent: fusibles, amperímetres i connectors. Cablejat elèctric iposta en funcionament.d) Disseny, muntatge elèctric i programació de la unitat de control.Selecció del PLC S7300Escollir el tipus de comunicacions que es realitzaran tant amb la unitat depotència com amb el PC.Disseny plànols elèctrics mitjançant el programa EPLAN.Mecanització, cablejat i posta en marxa del disseny elèctric.El disseny del software es realitzarà mitjançant l'eina de programacióSTEP7 de SiemensProgramació del PLC per poder treballar diferents tipus de moviments itrajectòriese) Disseny i programació de la interfície d'usuari des d'un PCProgramació d'una interfície gràfica mitjançant WinCC Flexible per tal quel'usuari només introduint dades pugui fer que el robot es mogui demanera manual o semiautomàtica . També s'ha programat per tal quegeneri trajectòries en mode automàtic.S'ha programat una illa de pick and place a mode d'exemplificació.

1.° Anonymi tractatus de algorismo, sive de arte numerandi : praemittuntur tractatus de numerorum mysteriis, et narratio Fratris Benedicti Aretini de indulgentia loco de Portiuncula concessa ab Honorio Papa III. — 2.° Magistri Joannis de Sacrobosco tractatus de computo. — 3.° Ejusdem tractatus de sphaera. — 4.° Theorica planetarum : authore Gerardo Carmonensi. — 5.° Anonymi explicationes allegoricae quorumdam Scripturae sacrae locorum : initium desideratur. — 6.° Elementorum Euclidis libri quinque priores. — 7.° Anonymi tractatus de speculis.

Colbertinus

Aprendiendo entre iguales, lema del III encuentro Forma Joven

Boletín semanal para profesionales sanitarios de la Secretaría General de Salud Pública y Participación Social de la Consejería de Salud

[Tête de jeune fille]. III : [estampe] ([3eme état en plusieurs plaques, imprimé en jaune, bleu et rouge]) / [gravé sous la direction de Jacob Christoph Le Blon] ; [d'après Carlo Maratti ?]

Référence bibliographique : Singer, 45