Carcinome métaplasique du sein : à propos d’un cas

Le carcinome métaplasique du sein est une tumeur maligne primaire rare et agressive, représentant 0,2-5% de tous les cancers du sein. Cette tumeur maligne est caractérisée par la présence histologique d'au moins deux types cellulaires, généralement des composants épithéliaux et mésenchymateux. Nous rapportons le cas d’une patiente qui présentait un carcinome métaplasique du sein droit. A travers ce cas et une revue de la littérature, les caractéristiques anatomo-cliniques, radiologiques, thérapeutiques et évolutives seront discutées.Les variantes métaplasiques sont agressives, chimiorésistantes et ont une forte propension à métastaser ainsi qu’un risque de récidive locale plus élevé, rendant ainsi leur pronostic plus sombre que les carcinomes du sein non métaplasiques c'est-à-dire, les carcinomes canalaires invasifs. Même si les carcinomes métaplasiques du sein sont traités de la même manière que les carcinomes invasifs, il n’en reste pas moins que leur prise en charge reste difficile et qu’il n’existe pas de standard thérapeutique. Le principal traitement reste la chirurgi

Microfluidic active loading of single cells enables analysis of complex clinical specimens

A fundamental trade-off between flow rate and measurement precision limits performance of many single-cell detection strategies, especially for applications that require biophysical measurements from living cells within complex and low-input samples. To address this, we introduce ‘active loading’, an automated, optically-triggered fluidic system that improves measurement throughput and robustness by controlling entry of individual cells into a measurement channel. We apply active loading to samples over a range of concentrations (1–1000 particles μL[superscript −1]), demonstrate that measurement time can be decreased by up to 20-fold, and show theoretically that performance of some types of existing single-cell microfluidic devices can be improved by implementing active loading. Finally, we demonstrate how active loading improves clinical feasibility for acute, single-cell drug sensitivity measurements by deploying it to a preclinical setting where we assess patient samples from normal brain, primary and metastatic brain cancers containing a complex, difficult-to-measure mixture of confounding biological debris.National Cancer Institute (U.S.) (R01 CA170592)National Cancer Institute (U.S.) (R33 CA191143)National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051)Bridge Projec

Microfluidic active loading of single cells enables analysis of complex clinical specimens

A fundamental trade-off between flow rate and measurement precision limits performance of many single-cell detection strategies, especially for applications that require biophysical measurements from living cells within complex and low-input samples. To address this, we introduce ‘active loading’, an automated, optically-triggered fluidic system that improves measurement throughput and robustness by controlling entry of individual cells into a measurement channel. We apply active loading to samples over a range of concentrations (1–1000 particles μL[superscript −1]), demonstrate that measurement time can be decreased by up to 20-fold, and show theoretically that performance of some types of existing single-cell microfluidic devices can be improved by implementing active loading. Finally, we demonstrate how active loading improves clinical feasibility for acute, single-cell drug sensitivity measurements by deploying it to a preclinical setting where we assess patient samples from normal brain, primary and metastatic brain cancers containing a complex, difficult-to-measure mixture of confounding biological debris.National Cancer Institute (U.S.) (R01 CA170592)National Cancer Institute (U.S.) (R33 CA191143)National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051)Bridge Projec

Bio-efficacy of hydroxy-selenomethionine as a selenium supplement in pregnant dairy heifers and on the selenium status of their calves

This study aimed to determine the effects of supplementing pregnant heifers with the organic selenium source 2-hydroxy-4-methylselenobutanoic acid (HMSeBA) during last eight weeks of pregnancy on dam and calf Se status. A total of 42 in-calf heifers were recruited to the study and randomly allocated to one of three treatments; a negative control (Con), sodium selenite (NaSe) or HMSeBA. Animals were blocked by body weight, body condition score, and expected calving date prior to treatment allocation. Following enrollment all animals underwent a seven week wash-out period after which they received their respective supplements, topped dressed daily onto a basal diet for the last eight weeks of pregnancy. Heifer blood samples were taken at weekly intervals from enrollment until two weeks before expected calving date, and as soon as possible after calving for determination of whole blood glutathione peroxidase activity (GSH-Px) and plasma selenium (Se) and malondealdehyde (MDA) concentrations. Selenized amino acids were determined in plasma samples taken at three weeks pre-calving. A colostrum sample was taken as close to parturition as possible for determination of colostrum total Se, selenized amino acid, and Immunoglobulin G (IgG) concentration. Calves were blood sampled as close to birth as possible for determination of whole blood GSH-Px activity and plasma Se and MDA concentration. Differences in whole blood GSH-Px activity did not become apparent until calving; GSH-Px activity was lowest in Con heifers (P < 0.05) but similar between NaSe and HMSeBA. Plasma Se was lowest in unsupplemented heifers and greatest in those supplemented with HMSeBA (P < 0.001) and this was attributable to greater selenomethionine concentrations in the plasma of HMSeBA heifers (P < 0.01). Colostrum Se was lowest in Con heifers and greatest in HMSeBA (P < 0.001), the greater Se concentration of HMSeBA heifers was attributable to a greater proportion of total Se comprising selenocysteine (P = 0.061), the reason for this is not known. There was no effect of supplementation on colostrum IgG concentration. Plasma Se was lowest in those calves born to Con heifers and greatest in those born to HMSeBA heifers (P < 0.001). There were no effects of treatment on calf whole blood GSH-Px activity or plasma MDA concentration. The enhanced Se status associated with HMSeBA supplementation is likely a consequence of selenomethionine supply and may confer benefits to both the dam and her calf post-partum

Metabolomics with LC-QTOF-MS Permits the Prediction of Disease Stage in Aortic Abdominal Aneurysm Based on Plasma Metabolic Fingerprint

Abdominal aortic aneurysm (AAA) is a permanent and localized aortic dilation, defined as aortic diameter ≥3 cm. It is an asymptomatic but potentially fatal condition because progressive enlargement of the abdominal aorta is spontaneously evolving towards rupture

Porphyromonas gingivalis Participates in Pathogenesis of Human Abdominal Aortic Aneurysm by Neutrophil Activation. Proof of Concept in Rats

International audienceBACKGROUND: Abdominal Aortic Aneurysms (AAAs) represent a particular form of atherothrombosis where neutrophil proteolytic activity plays a major role. We postulated that neutrophil recruitment and activation participating in AAA growth may originate in part from repeated episodes of periodontal bacteremia. METHODS AND FINDINGS: Our results show that neutrophil activation in human AAA was associated with Neutrophil Extracellular Trap (NET) formation in the IntraLuminal Thrombus, leading to the release of cell-free DNA. Human AAA samples were shown to contain bacterial DNA with high frequency (11/16), and in particular that of Porphyromonas gingivalis (Pg), the most prevalent pathogen involved in chronic periodontitis, a common form of periodontal disease. Both DNA reflecting the presence of NETs and antibodies to Pg were found to be increased in plasma of patients with AAA. Using a rat model of AAA, we demonstrated that repeated injection of Pg fostered aneurysm development, associated with pathological characteristics similar to those observed in humans, such as the persistence of a neutrophil-rich luminal thrombus, not observed in saline-injected rats in which a healing process was observed. CONCLUSIONS: Thus, the control of periodontal disease may represent a therapeutic target to limit human AAA progression

DNA repair deficiency sensitizes lung cancer cells to NAD+ biosynthesis blockade.

Synthetic lethality is an efficient mechanism-based approach to selectively target DNA repair defects. Excision repair cross-complementation group 1 (ERCC1) deficiency is frequently found in non-small-cell lung cancer (NSCLC), making this DNA repair protein an attractive target for exploiting synthetic lethal approaches in the disease. Using unbiased proteomic and metabolic high-throughput profiling on a unique in-house-generated isogenic model of ERCC1 deficiency, we found marked metabolic rewiring of ERCC1-deficient populations, including decreased levels of the metabolite NAD+ and reduced expression of the rate-limiting NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT). We also found reduced NAMPT expression in NSCLC samples with low levels of ERCC1. These metabolic alterations were a primary effect of ERCC1 deficiency, and caused selective exquisite sensitivity to small-molecule NAMPT inhibitors, both in vitro - ERCC1-deficient cells being approximately 1,000 times more sensitive than ERCC1-WT cells - and in vivo. Using transmission electronic microscopy and functional metabolic studies, we found that ERCC1-deficient cells harbor mitochondrial defects. We propose a model where NAD+ acts as a regulator of ERCC1-deficient NSCLC cell fitness. These findings open therapeutic opportunities that exploit a yet-undescribed nuclear-mitochondrial synthetic lethal relationship in NSCLC models, and highlight the potential for targeting DNA repair/metabolic crosstalks for cancer therapy