23 research outputs found
Eliminación de formaldehído mediante CWO
Se sintetizaron catalizadores en polvo y en membrana de óxidos mixtos de Co-Cu-Ce soportados en Al₂O₃ comercial en polvo y en una membrana inorgánica de γ-Al₂O₃ como soporte. Los catalizadores fueron caracterizados por Difracción de Rayos X, Microscopia Electrónica de Barrido y Estudio de Análisis Químico Elemental. Para evaluar la eficiencia de los materiales catalíticos impregnados con los óxidos mixtos se realizaron estudios de actividad catalítica para la Oxidación Húmeda Catalítica (CWO) de una solución de formaldehído con concentración de 500 ppm en un reactor de tanque agitado, con flujo continuo de la fase oxidante.In this paper, powder catalysts and mixed oxide membrane Co-Cu-Ce supported on Al₂O₃ commercial powder and an inorganic membrane were synthesized γ-Al₂O₃ as support. The catalysts were characterized by X-ray diffraction, scanning electron microscopy and Chemical Elemental Analysis Study. Catalytic activity studies for Catalytic Wet Oxidation (CWO) of formaldehyde solution with a concentration of 500 ppm in slurry stirred tank reactor type, with continuous flow of the oxidizing phase
Neoadjuvant intralesional methotrexate for juvenile xanthogranuloma in an adult
Juvenile xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis usually occurring in infants and typically located in the head or neck.1 Clinically, solitary skin lesions are found in 60%–82% of patients and the most common variant is characterized by one yellowish nodule. Adult onset is rare, and although JXG is usually self-limiting in children, spontaneous resolution is uncommon at older ages. In addition, up to 50% of patients with spontaneous regression develop an atrophy or anetodermal area.2 Thus, complete excision is frequently performed in this population subgroup to achieve better cosmetic results. In disseminated forms, different chemotherapy regimens, corticosteroids and other systemic therapies are used. Herein, we report a case of adult JXG treated with intralesional methotrexate (MTX) resulting in a rapid reduction in size
A Summary of the Inaugural WHO Classification of Pediatric Tumors: Transitioning from the Optical into the Molecular Era.
Pediatric tumors are uncommon, yet are the leading cause of cancer-related death in childhood. Tumor types, molecular characteristics, and pathogenesis are unique, often originating from a single genetic driver event. The specific diagnostic challenges of childhood tumors led to the development of the first World Health Organization (WHO) Classification of Pediatric Tumors. The classification is rooted in a multilayered approach, incorporating morphology, IHC, and molecular characteristics. The volume is organized according to organ sites and provides a single, state-of-the-art compendium of pediatric tumor types. A special emphasis was placed on blastomas, which variably recapitulate the morphologic maturation of organs from which they originate. SIGNIFICANCE: In this review, we briefly summarize the main features and updates of each chapter of the inaugural WHO Classification of Pediatric Tumors, including its rapid transition from a mostly microscopic into a molecularly driven classification systematically taking recent discoveries in pediatric tumor genomics into account
Histone Acetylation-Mediated Regulation of the Hippo Pathway
The Hippo pathway is a signaling cascade recently found to play a key role in tumorigenesis therefore understanding the mechanisms that regulate it should open new opportunities for cancer treatment. Available data indicate that this pathway is controlled by signals from cell-cell junctions however the potential role of nuclear regulation has not yet been described. Here we set out to verify this possibility and define putative mechanism(s) by which it might occur. By using a luciferase reporter of the Hippo pathway, we measured the effects of different nuclear targeting drugs and found that chromatin-modifying agents, and to a lesser extent certain DNA damaging drugs, strongly induced activity of the reporter. This effect was not mediated by upstream core components (i.e. Mst, Lats) of the Hippo pathway, but through enhanced levels of the Hippo transducer TAZ. Investigation of the underlying mechanism led to the finding that cancer cell exposure to histone deacetylase inhibitors induced secretion of growth factors and cytokines, which in turn activate Akt and inhibit the GSK3 beta associated protein degradation complex in drug-affected as well as in their neighboring cells. Consequently, expression of EMT genes, cell migration and resistance to therapy were induced. These processes were suppressed by using pyrvinium, a recently described small molecule activator of the GSK 3 beta associated degradation complex. Overall, these findings shed light on a previously unrecognized phenomenon by which certain anti-cancer agents may paradoxically promote tumor progression by facilitating stabilization of the Hippo transducer TAZ and inducing cancer cell migration and resistance to therapy. Pharmacological targeting of the GSK3 beta associated degradation complex may thus represent a unique approach to treat cancer. © 2013 Basu et al
Biomass-modulated fire dynamics during the last glacial-interglacial transition at the central pyrenees (Spain)
Understanding long-term fire ecology is essential for current day interpretation of ecosystem fire responses. However palaeoecology of fire is still poorly understood, especially at high-altitude mountain environments, despite the fact that these are fire-sensitive ecosystems and their resilience might be affected by changing fire regimes. We reconstruct wildfire occurrence since the Lateglacial (14.7. cal. ka BP) to the Mid-Holocene (6. cal. ka BP) and investigate the climate-fuel-fire relationships in a sedimentary sequence located at the treeline in the Central Spanish Pyrenees. Pollen, macro- and micro-charcoal were analysed for the identification of fire events (FE) in order to detect vegetation post-fire response and to define biomass-fire interactions. mean fire intervals (mfi) reduced since the Lateglacial, peaking at 9-7.7. cal. ka BP while from 7.7 to 6. cal. ka BP no fire is recorded. We hypothesise that Early Holocene maximum summer insolation, as climate forcing, and mesophyte forest expansion, as a fuel-creating factor, were responsible for accelerating fire occurrence in the Central Pyrenees treeline. We also found that fire had long-lasting negative effects on most of the treeline plant communities and that forest contraction from 7.7. cal. ka BP is likely linked to the ecosystem's threshold response to high fire frequencies.This research has been funded by the projects DINAMO (CGL2009-07992) (funding EGPF — grant ref. BES-2010-038593 and MSC), DINAMO2 (CGL2012-33063), ARAFIRE (2012 GA LC 064), GRACCIE-CONSOLIDER (CSD2007-00067). GGR was funded by the Juan de la Cierva Program (grant ref. JCI2009-04345) and JAE-Doc CSIC Program, LLM was supported by a postdoctoral MINT fellowship funded by the Institute for the Environment (Brunel University), AMC is a Ramón y Cajal fellow (ref: RYC-2008-02431), APS holds a grant funded by the Aragon Government (ref. 17030G/5423/480072/14003) and JAE holds a grant funded by the Basque Country Government (BFI-2010-5)
The High Multiplicity of Prenatal (Congenital Type) Nevi in Adolescents and Adults
In the absence of work on prenatal nevogenesis, it has long been necessary to define congenital melanocytic nevi by clinical detection on neonatal skin examination. They are seen in approximately 1% of newborns, with multiplicity in approximately 3% of cases. Melan-A staining of grossly normal fetal skin recently demonstrated fetal nevi, whose features validated certain traditional histologic criteria for congenital type nevi that may not have been detectable at birth. This suggested that many clinically acquired nevi actually formed in utero, like congenital nevi. Prenatal nevi has been suggested as a preferred synonym for congenital type nevi. Prenatal nevi were detected in 6 of 25 fetuses (24%), a strikingly higher incidence than congenital nevi in newborns. In this series of 354 patients with prenatal (congenital type) nevi encountered in routine practice at a community hospital, over 30% of both adolescents and adults had multiple prenatal nevi; a strikingly higher rate of multiplicity than congenital nevi in newborns. This high multiplicity may reflect origin beneath the epidermis, with many prenatal nevi working their way up to the surface of the skin decades after birth
Targeting the GSK 3 beta associated destruction complex reduces TAZ levels, cancer cell migration and resistance to therapy.
<p><u>Panel A.</u> Naïve SW480 cells were exposed to conditioned medium from Belinostat (1 µM) treated counterparts (Bel-CM), in the absence or the presence of Pyrvinium (PYR) at 0.5 µM. After 24 hours, the cells were processed for Western blot with antibodies to TAZ, Vimentin (Vim) and beta actin. <u>Panel B.</u> Monolayer scratch assay depicting the effect of Bel-CM on cell migration and its delay by pyrvinium. MCF cells cultured until confluency and scratches introduces in the monolayer using a pipette tip. The cells were then incubated in the presence or absence of Bel-CM, with or without pyrvinium (0.5 µM) for the indicated times, representative photographs are shown. <u>Panel C.</u> Effect of Bel-CM and pyrvinium of cellular response to doxorubicin. SW480 cells were incubated with doxorubicin at the indicated concentration in absence or presence of Bel-CM, Pyrvinium (PYR) or both. Cell viability was determined by MTT assay as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062478#s2" target="_blank">Methods</a> section and the data represented as <i>per cent</i> of control non-treated cells. The data represent average of three determinations ±SE. Statistical significance is shown for Bel-CM exposed cells in the absence or the presence of PYR (**p<0.001). <u>Panel D.</u> Effect of PYR on cellular response to other drugs. Cells were exposed to the indicated drugs in the absence or presence of Bel-CM (BCM) and pyrvinium (P). Cell viability was determined by MTT assay after 72 hours in culture. The data represent average of three determinations ±SE. Statistical significance is shown for Bel-CM exposed cells in the absence or the presence of PYR for each drug tested (*p<0.05, **p<0.001).</p
Role of secreted growth factors and cytokines in mediating Belinostat-induced activation of the Hippo pathway.
<p><u>Panel A.</u> SW480 cells were incubated with the indicated concentrations of Belinostat for 24 hours and expression levels of selected secreted factors were determined by QPCR and compared to those in control non-treated cells. <u>Panel B.</u> Effect of individual growth factors and cytokines on TAZ levels and phosphorylation of GSK 3 beta. Cells were incubated with the indicated soluble factors (at 100 ng/ml each) for 24 hours and proteins extracted and processed for western blot using specific antibodies to TAZ and phosphorylated GSK3 beta. <u>Panel C.</u> Effect of individual growth factors and cytokines on activity of the Hippo reporter. Cells transfected with the reporter construct were incubated with the indicated factors for 24 hours and luciferase activity measured as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062478#s2" target="_blank">Methods</a> section. Each bar in Panels A and C represents the average of three determinations ±SE. Statistical significance is shown for treated cells compared to the corresponding untreated controls (*p<0.05, **p<0.001).</p
Schematic model depicting nuclear regulation of the Hippo pathway in drug-affected and neighboring cells.
<p>Exposure to certain drugs affecting DNA or chromatin results in enhanced expression of secreted growth factors and cytokines. These secreted factors (SFs) may in turn signal in autocrine/paracrine manner for activation of Akt and inhibition of GSK3 beta associated degradation complex (GSK3β/DC) resulting in stabilization of TAZ oncogene. Consequently, expression of EMT genes is enhanced, leading to increased cell migration and drug resistance (DR) in both drug affected and neighboring cells. These processes can be overcome by using pyrvinium (PYR), a pharmacological activator of GSK3 beta associated degradation complex.</p
Respective roles of DNA damage and chromatin modification in regulation of the Hippo pathway.
<p><u>Panel A</u>. Hippo reporter activity in response to drugs tested at concentrations that induce 50% inhibition of proliferation in SW480 cells (indicated at the top of each bar). Ctl: control., Cisp: cisplatin., Dox: doxorubicin., Bel: Belinostat., TSA: Trichostatin A., AZA: 5 Azacitidine(decitabine)). <u>Panel B.</u> Western blot showing the effect of Belinostat on acetylation of Histone H3 at Lysine 9 (H3K9) (Upper level), and activity of Hippo reporter in MCF7 and WM 266 melanoma cells. Each bar in Panels A and B represents the average of three determinations ±SE. Statistical significance is shown for drug-treated cells compared to the corresponding untreated controls (*p<0.05, **p<0.001). <u>Panel C.</u> Western blots depicting the effect of Belinostat on expression and/or phosphorylation of various components of the Hippo pathway in SW480 cells. <u>Panel D.</u> Expression of TAZ in MCF7 and WM 266 cells in response to Belinostat. <u>Panel E.</u> Representative data showing the effect of siRNA mediated Knockdown of HDAC1 on expression of TAZ in WM266 cells measured by Western blot.</p