Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids

International audienceThe worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary car-cinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low-and high-grade lung neuroendocrine neoplasms

Contribution a l'etude du transport intestinal du fer : localisation d'un transporteur potentiel : la lacto-ferrine

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Preparative laser capture microdissection and single-pot cell wall material preparation: a novel method for tissue-specific analysis.

International audienceIn adaptation to their function the walls of plant cell display tissue-specific variations of composition according to their developmental stage, cell type and stress of various origin. It is therefore important to obtain a precise analytical data describing the cell wall composition with respect to these different factors. In the present work, laser capture microdissection (LCM) was used for isolating different tissues from the stem of Urtica dioica L. at a semi-preparative scale. The technique was associated for the first time to a one-pot sequential cell wall preparation and hydrolysis for the carbohydrate analysis of each cell type. The results demonstrate that the combination of LCM and micro-analytical methods can provide individual cell type composition and should improve our knowledge of the biochemical diversity of cell walls in plants. This approach will be of potential interest for the understanding of the effects of stress or genetic engineering on the composition of the cell walls

Morphometric studies of collagen and fibrin lattices contracted by human gingival fibroblasts; comparison with dermal fibroblasts.

Cell shape variations and substratum re-organization during contraction of floating collagen and fibrin lattices seeded with human gingival fibroblasts were determined by computerized image analysis of light and scanning electron microscopic images. Data were compared with those obtained with lattices populated with human dermal fibroblasts. The extent of collagen lattice contraction was similar with both cell types, resulting in a two-fold decrease in the area fractions occupied by collagen fibers. Fibroblasts exhibited a rounded shape (form factors equal to 0.8 and 0.7 for gingival and dermal cells, respectively) at day 1 of culture; they possessed a more elongated appearance (with form factors equal to 0.3 and 0.15 for gingival and dermal cells, respectively) at day 7. Continuous (gingival) and discontinuous (dermal) layers of cells were evidenced at the cortex of lattices. Contractions were associated with a significant reduction of the diameters of collagen fibers. Re-organization of substratum, as analyzed by the "Rose of Directions" technique, was evidenced only at the vicinity of filopodia where fibers ran parallel to these protrusions. Several lysed matrix cavities were observed when fibrin lattices were populated with gingival but not dermal fibroblasts at day 5 of culture. Although cells in fibrin lattices exhibited morphometric parameters comparable with those in collagen lattices, no fibroblast layers could be demonstrated at gel peripheries. Fibrin matrices consisted of an isotropic network of entangled fibrin filaments from the start of culture, and only a slight reduction of the diameters of fibrin fibers could be evidenced in dermal fibroblast-populated lattices. Fibrinolysis at the vicinity of gingival fibroblasts led to an entire re-organization of substratum toward the formation of larger fibers. The differential behavior of gingival vs. dermal fibroblasts inside fibrin but not collagen matrices could therefore partly explain the increased rate of remodeling of gingiva as compared with dermis

The rate of fibrinolysis is increased by free retraction of human gingival fibroblast populated fibrin lattices.

We previously demonstrated that human gingival fibroblasts (HGF), but not their dermal counterparts, when seeded in retracting fibrin lattices induced intense fibrinolysis that was observed at the earliest stages of contraction and led to complete matrix degradation by day 7 of culture. Our aim was to examine the influence of mechanical forces in such fibrinolytic processes. HGF were seeded in retracting (R) e.g. free floating or non retracting (NR) e.g. anchored fibrin lattices (FL). Cultures were analysed from day 1-12 by phase contrast microscopy and scanning electron microscopy (s.e.m.). Levels of fibrin degradation products (FDP) and tissue plasminogen activator (tPA) accumulating in culture media were quantified by ELISA. Urokinase (uPA) and gelatinase A (MMP2) were identified by zymographic techniques. At the s.e.m. level, vacuolization around some HGF was noticed at the earliest stages of culture for RFL and complete degradation of lattices occurred at day 7. Formation of lysed matrix cavity was far less intense in NRFL even after 12 days of culture. FDP amounts at day 4 of culture were equal to 79 +/- 14 and 8.5 +/- 0.6 micrograms/10(5) cells for RFL and NRFL, respectively; tPA levels were equal to 5.8 +/- 0.6 (RFL) and 2.1 +/- 0.3 ng/10(5) cells (NRFL) and differences were still evident at day 7. The kinetics of tPA production were identical in either retracting fibrin or collagen lattices. On the contrary, uPA and proMMP2 productions were similar in RFL and NRFL. Isometric forces, but not the matrix support, were responsible for accelerated tPA production and fibrinolysis in HGF populated lattices

Pain characterization and response to palliative care in dogs with naturally-occurring appendicular osteosarcoma: An open label clinical trial.

This study aimed to characterize bone cancer pain (quantitative sensory testing (QST), stance asymmetry index, actimetry, scores of pain and quality of life (QoL)) in dogs with appendicular osteosarcoma (OSA), and to evaluate a stepwise palliative analgesic treatment. The pain profile of thirteen client-owned dogs with OSA was compared with seven healthy dogs. Dogs with OSA were then enrolled in a prospective, open-label, clinical trial. Outcome measures included: primary and secondary mechanical thresholds (MT), conditioned pain modulation (CPM), stance asymmetry index, actimetry (most and least active periods), visual analog scales and QoL. After baseline assessments, stepwise treatment comprised orally administered cimicoxib (2 mg/kg q 24h), amitriptyline (1-1.5 mg/kg q 24h) and gabapentin (10 mg/kg q 8h); re-evaluations were performed after 14 (D14), 21 (D21) and 28 (D28) days, respectively. Statistics used mixed linear models (α = 5%; one-sided). Centralized nociceptive sensitivity (primary and secondary MT, and dynamic allodynia) was recorded in OSA dogs. Healthy dogs had responsive CPM, but CPM was deficient in OSA dogs. Construct validity was observed for the QST protocol. Asymmetry index was significantly present in OSA dogs. The CPM improved significantly at D14. When compared with baseline (log mean ± SD: 4.1 ± 0.04), most active actimetry significantly improved at D14 (4.3 ± 0.04), D21 and D28 (4.2 ± 0.04 for both). When compared with baseline, least active actimetry significantly decreased after treatment at all time-points indicating improvement in night-time restlessness. No other significant treatment effect was observed. Except for tactile threshold and actimetry, all outcomes worsened when gabapentin was added to cimicoxib-amitriptyline. Dogs with bone cancer are affected by widespread somatosensory sensitivity characterized by peripheral and central sensitization and have a deficient inhibitory system. This severe pain is mostly refractory to palliative analgesic treatment, and the latter was only detected by specific and sensitive outcomes

Expérience faite à Versaille, en présence de leurs Majestés et de la Famille Royale, par Mr. Montgolfier, le 19. Sept. 1783. La Machine Aérostatique avoit 57 pieds de haut, sur 41 de diamètre : [estampe] / Dessiné par le Chr. de Lorimier ; Gravé par N. De Launay ; [vers de] Mr. Gudin de la Brunellerie

Référence bibliographique : Mondin, 5