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Le Touquet – Paris-Plage, France

Handra-Luca A.,University of Lille Nord de France | Handra-Luca A.,University of Paris 13 | Lesty C.,Center dEcologie Cellulaire | Hammel P.,Service de Gastroenterologie | And 16 more authors.
Pancreas | Year: 2012

OBJECTIVES: The aims of this study were to study the biological and clinical significance of 3 main proteins of the mitogen-activated protein kinase (MAPK) signaling pathway, ERK1/2, P38, and MKK4, in a series of patients having pancreatic adenocarcinomas treated by surgery. METHODS: We examined the immunohistochemical expression of 3 MAPK proteins, ERK1/2, P38, and MKK4 in 99 surgically resected pancreatic ductal adenocarcinomas. Tumor protein expression was studied with regard to pathological characteristics and to postsurgical recurrence-free and overall survivals. RESULTS: MKK4 expression was related to tumor cell proliferation, evaluated by the Ki67 index (P < 0.01). ERK1/2 expression was related to a shorter recurrence-free survival on both univariate and multivariate analysis (P < 0.01; odds ratio, 8.39; 95% confidence interval, 2.68-26.26) independently of lymph node metastases and tumor size, and to a shorter overall survival (P = 0.01) on univariate analysis. In patients without postsurgical treatment, both ERK1/2 and P38 tumor expression correlated with a shorter recurrence-free survival (P < 0.01 and P = 0.02, respectively). CONCLUSIONS: The results of our study suggest that in pancreatic ductal adenocarcinomas, the MKK4 protein was directly related to high cell proliferation, and that tumor ERK1/2 and P38 expression correlated to shorter postsurgical recurrence-free and overall survivals. © 2012 Lippincott Williams & Wilkins, Inc. Source


Yipp B.G.,University of Calgary | Petri B.,University of Calgary | Salina D.,University of Calgary | Jenne C.N.,University of Calgary | And 11 more authors.
Nature Medicine | Year: 2012

Neutrophil extracellular traps (NETs) are released as neutrophils die in vitro in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, we directly visualized live polymorphonuclear cells (PMNs) in vivo rapidly releasing NETs, which prevented systemic bacterial dissemination. NETosis occurred during crawling, thereby casting large areas of NETs. NET-releasing PMNs developed diffuse decondensed nuclei, ultimately becoming devoid of DNA. Cells with abnormal nuclei showed unusual crawling behavior highlighted by erratic pseudopods and hyperpolarization consistent with the nucleus being a fulcrum for crawling. A requirement for both Toll-like receptor 2 and complement-mediated opsonization tightly regulated NET release. Additionally, live human PMNs injected into mouse skin developed decondensed nuclei and formed NETS in vivo, and intact anuclear neutrophils were abundant in Gram-positive human abscesses. Therefore early in infection NETosis involves neutrophils that do not undergo lysis and retain the ability to multitask. © 2012 Nature America, Inc. All rights reserved. Source


Lesty C.,Center dEcologie Cellulaire | Baudet S.,Center dEcologie Cellulaire | Charlotte F.,Laboratory of Anatomic Pathology
Analytical and Quantitative Cytology and Histology | Year: 2010

OBJECTIVE: To use a purely geometric data-unravelling method to identify, without a priori, direct links of neoangiogenesis with known clinicobiologic variables in 23 untreated chronic lymphocytic leukemia (CLL) patients at the time of marrow sampling. STUDY DESIGN: We measured neovascular surface density (CD34 endothelial marker) in the 10 most labeled fields (hVA), cellularity (CA) and the percentage of avascular fields (AVF) in bone marrow biopsy specimens from 34 patients with CLL. Vascular endothelial growth factor (VEGF) was assayed in thawed serum samples from 8 of the 23 untreated patients (12 Rai stage 0, 6 Rai stage I-II, 5 Binet stage B-C). RESULTS: Neoangiogenesis hVA was lower in the 12 stage O patients (p<0.039) and in the 6 patients with nodular interstitial mixed infiltration (p=0.058). The link between hVA and serum VEGF (sVEGF) was negative in 8 patients (R=-0.49, -0.70 for a given age). Age was linked to moderate interstitial infiltration (p<0.02), AVF (R=0.37) and lower sVEGF levels (R=-0.676). The blood platelet count showed numerous correlations, including links with AVF (R = 0.40), low hVA (R = -0.38), female sex (p=0.068), absence of splenomegaly (p < 0.001), mixed-type infiltration (p < 0.01) and sVEGF (R=0.38, 0.61 for a given age). CONCLUSION: The links revealed by the iconography of correlations were described statistically. Surprisingly, negative links of hVA with the sVEGF level, 2 known prognostic factors, on the one hand, and with the blood platelet count, on the other hand, were found. The direct link between disease progression and the amount of avascular hematopoietic tissue (NS), not previously described, will require further study. Age should be taken into account. © Science Printers and Publishers, Inc. Source


Malawista S.E.,Yale University | Malawista S.E.,Center dEcologie Cellulaire | Chevance de Boisfleury A.,Center dEcologie Cellulaire
PLoS ONE | Year: 2013

In studying phagocytosis of zymosan particles by human blood monocytes in phase-contrast videomicroscopy, we found that monocytes loaded with zymosan particles became chemotactic for polymorphonuclear leukocytes (PMN) which closed on them and purloined their particle content. This despoliation usually occurred in monocytes that had begun to swell-prefiguring their death. The violent seizure of their contents by the aggressing PMN often tore the monocytes apart. However, some apparently healthy monocyte survived the removal of zymosan content by PMN or, more commonly, its removal by another monocyte. PMN-a much hardier cell in slide preparations-that were similarly loaded with zymosan particles, also attracted PMN. The latter could remove zymosan from the target cell without killing it. Thus, leukocytes were sacrificing significant portions of themselves without losing residual membrane integrity and motile function. Their behavior with respect to other particles (e.g., bacteria) will be of interest. We suggest that the membrane fusagen resides in the inner membrane leaflets when they are brought together in an extreme hourglass configuration. This event may be similar to the fragmentation of erythrocytes into intact pieces, the formation of cytokineplasts, the rear extrusion of content by migrating cells on surfaces, and the phagocytic process itself. © 2013 Malawista, Chevance de Boisfleury. Source


Malawista S.E.,Yale University | Malawista S.E.,Center dEcologie Cellulaire | Chevance De Boisfleury A.,Center dEcologie Cellulaire
FASEB Journal | Year: 2011

This is a discussion of acute gouty arthritis, seen for over 50 years of engagement. It addresses the evolution of our current understanding of the interaction between urate crystals and key cellular components of the gouty inflammatory paroxysm, with new material on pathogenesis. © FASEB. Source

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