Chloroquine supplementation increases the cytotoxic effect of curcumin against Her2/neu overexpressing breast cancer cells in vitro and in vivo in nude mice while counteracts it in immune competent mice

Autophagy is usually a pro-survival mechanism in cancer cells, especially in the course of chemotherapy, thus autophagy inhibition may enhance the chemotherapy-mediated anti-cancer effect. However, since autophagy is strongly involved in the immunogenicity of cell death by promoting ATP release, its inhibition may reduce the immune response against tumors, negatively influencing the overall outcome of chemotherapy. In this study, we evaluated the in vitro and in vivo anti-cancer effect of curcumin (CUR) against Her2/neu overexpressing breast cancer cells (TUBO) in the presence or in the absence of the autophagy inhibitor chloroquine (CQ). We found that TUBO cell death induced by CUR was increased in vitro by CQ and slightly in vivo in nude mice. Conversely, CQ counteracted the Cur cytotoxic effect in immune competent mice, as demonstrated by the lack of in vivo tumor regression and the reduction of overall mice survival as compared with CUR-treated mice. Immunohistochemistry analysis revealed the presence of a remarkable FoxP3 T cell infiltrate within the tumors in CUR/CQ treated mice and a reduction of T cytotoxic cells, as compared with single CUR treatment. These findings suggest that autophagy is important to elicit anti-tumor immune response and that autophagy inhibition by CQ reduces such response also by recruiting T regulatory (Treg) cells in the tumor microenvironment that may be pro-tumorigenic and might counteract CUR-mediated anti-cancer effects

Cálculo de la probabilidad absoluta de una nueva erupción en la isla de Ischia (Italia)

Ischia es la isla mayor y más poblada del archipiélago napolitano. Forma parte del complejo volcánico de la costa centro-occidental italiana y su actividad está relacionada con la presencia de fracturas profundas, asociadas a la apertura del mar Tirreno la cual comenzaba hace diez millones de años. El registro de varias erupciones históricas pone de manifiesto la posibilidad de que en un futuro no lejano se pueda producir un nuevo evento volcánico.El cálculo de dicha probabilidad representa una estimación esencial para evaluar adecuadamente el impacto que puede ocasionar el que se reanude la actividad volcánica en la isla; de hecho, en un posterior artículo, los resultados alcanzados en el presente estudio se emplearán para evaluar el riesgo volcánico en Ischia.Una de las pautas de análisis ha previsto la reconstrucción de un registro de las erupciones que se han verificado en los últimos 55.000 años; esta fecha coincide con la emisión del Tufo Verde, una de las unidades estratigráficas más importantes que conforman la isla de Ischia. Tomando como referencia al esquema de clasificación propuesto por Newhall y Self (1982), a cada erupción se le ha asignado un índice de intensidad, VEI, de manera que se divida todo el registro en clases. A continuación, mediante la aplicación de la estadística de Poisson, se ha determinado la probabilidad absoluta con la cual se puede producir un evento volcánico de cada clase de VEI en un intervalo de tiempo de 10 años.Si bien los resultados ponen de manifiesto que el valor de la probabilidad de erupción no es alto, éste no se debería subestimar, sobre todo en relación a dos características peculiares de este territorio que influyen directamente sobre el grado de riesgo volcánico: el elevado flujo turístico que recibe y el carácter insular.The isle of Ischia is the largest and the more populous of the Neapolitan Archipelago. It forms part of the volcanic complex of the middle-western Italian coast and its activity is related to the presence of deep fractures, associated to the aperture of the Tirreno sea, which began ten million years ago. The record of several historical eruptions reflects the possibility that in the future not so far could be produced a new volcanic event.The calculation of this possibility represents an essential estimation to evaluate adecuately the impact that can be occasioned when the volcanic activity starts again in the isle; in fact, in a next paper, the results reached in the present study will be used to evaluate the volcanic risk in Ischia.One of the aspects of analyses has taken into account the reconstruction of a recorder of eruptions that have been verified in the last 55.000 years, this date coincides with the emission of the Tufo Verde, one of the classification scheme proposed by Newhall and Self (1982), to each eruption has been assigned a intensity index, VEI, in order to divide all the record of classes. As follows, by applying the Poisson’s statistics, it has determined the absolute probability with which it can be produced a volcanic event of each class of VEI in a lapse of time of ten years.The results reflect that the value of probability of eruption is not high; however, is should no be underestimated, specially with respect to two peculiar characteristics of this territory that influxes directly on the grade of volcanic risk: its high touristy flux and its insular character

Evaluación del riesgo volcánico en la Isla de Ischia (Italia)

The volcanic activity of the isle of Ischia is Unmarked in the recent geological hisrory of the tirrenic area, during which, since ten million years ago, it has produced a process of migration in direction SW of the Italan peninsula, responsible of the formation of deep fractures by which magma has been injected to the surface.In this paper is realized a first approxomation to the evaluation of the volcanic risk in this isle, considering for this the dangerous of the potential eruptive process, the elements in risk and the vulnerability of these elements in fornt of the volcanic phenomenon.The analyses of the dangerous is based not only in the calculation of the probability that a new eruption occurs in a determined zone of the isle, but also in the estimation of the probalility with which the different eruptive phenomenology occurred. These typologies conditioned also the value of the vulnerability of the elements of territory, because the destruction level that will produce is different. When the parameter of dangerous is estimated the results of a previous study has been taken into account, in which the probability of occurrence of a new eruption in the isle had been calculated.In spite of the grade of risk is not so high, it should not be underestimated in function of two peculiar characteristics of this territory: its high touristy flux and its insular character.La actividad volcánica de la isla de Ischia se enmarca en la reciente historia geológica del área tirrénica, en el transcurso de la cual, desde hace diez millones de años, se ha producido un proceso de migración en dirección Sureste de la península italiana, responsable de la formación de profundas fracturas a través de las cuales se ha inyectado magma hacia la superficie.En este artículo se realiza una primera aproximación a la evaluación del riesgo volcánico en la isla, considerando para ello la peligrosidad del potencial proceso eruptivo, los elementos en riesgo y la vulnerabilidad de dichos elementos ante el fenómeno volcánico.El análisis de la peligrosidad se basa no sólo en el cálculo de la probabilidad de que tenga lugar una nueva erupción en una zona determinada de la isla, sino también en la estimación de la probabilidad con la que se desarrollarían las distintas fenomenologías eruptivas. Dichas tipologías condicionan a su vez el valor de la vulnerabilidad de los elementos del territorio, ya que el nivel de destrucción que provocarían es distinto. Al estimar el parámetro de la peligrosidad se han tenido en cuenta los resultados de un estudio precedente, en el cual se había calculado la probabilidad de ocurrencia de una nueva erupción en la isla.A pesar de que el grado de riesgo no es elevado, se argumenta que éste no debería subestimarse en función de dos características peculiares de este territorio: el elevado flujo turístico que recibe y la insularidad

GaAs(110) surface electronic structure by metastable deexcitation spectroscopy

Metastable deexcitation spectroscopy was applied to study the surface valence electronic structure of clean cleaved GaAs(110). Metastable deexcitation spectroscopy was flanked by angle-resolved photoemission. An effective surface density of states was derived from the experimental spectrum through deconvolution. Two groups of states were observed in the 0-4 and 5-8 eV range of binding energy, respectively. These features were ascribed to emission from surface states. A plane-by-plane tight-binding density-of-states calculation was performed. More quantitative insights were obtained by comparing experimental and theoretical results. The most prominent feature of the first group of states of deconvolution was assigned to surface state A(5). Contributions from states A(4), A(3), A(1)', and A(2)' were also observed. The doublet of the second group of features was identified with C-2 and C-1. Relative amplitudes of effective surface density of states were related to surface charge density

Ion counting efficiencies at the IGISOL facility

At the IGISOL-JYFLTRAP facility, fission mass yields can be studied at high precision. Fission fragments from a U target are passing through a Ni foil and entering a gas filled chamber. The collected fragments are guided through a mass separator to a Penning trap where their masses are identified. This simulation work focuses on how different fission fragment properties (mass, charge and energy) affect the stopping efficiency in the gas cell. In addition, different experimental parameters are varied (e. g. U and Ni thickness and He gas pressure) to study their impact on the stopping efficiency. The simulations were performed using the Geant4 package and the SRIM code. The main results suggest a small variation in the stopping efficiency as a function of mass, charge and kinetic energy. It is predicted that heavy fragments are stopped about 9% less efficiently than the light fragments. However it was found that the properties of the U, Ni and the He gas influences this behavior. Hence it could be possible to optimize the efficiency.Comment: 52 pages, 44 figure

In vitro and in vivo inhibition of breast cancer cell growth by targeting the Hedgehog/GLI pathway with SMO (GDC-0449) or GLI (GANT-61) inhibitors.

Aberrant Hedgehog (Hh)/glioma-associated oncogene (GLI) signaling has been implicated in cancer progression. Here, we analyzed GLI1, Sonic Hedgehog (Shh) and NF-κB expression in 51 breast cancer (ductal carcinoma) tissues using immunohistochemistry. We found a positive correlation between nuclear GLI1 expression and tumor grade in ductal carcinoma cases. Cytoplasmic Shh staining significantly correlated with a lower tumor grade. Next, the in vitro effects of two Hh signaling pathway inhibitors on breast cancer cell lines were evaluated using the Smoothened (SMO) antagonist GDC-0449 and the direct GLI1 inhibitor GANT-61. GDC-0449 and GANT-61 exhibited the following effects: a) inhibited breast cancer cell survival; b) induced apoptosis; c) inhibited Hh pathway activity by decreasing the mRNA expression levels of GLI1 and Ptch and inhibiting the nuclear translocation of GLI1; d) increased/decreased EGFR and ErbB2 protein expression, reduced p21- Ras and ERK1/ERK2 MAPK activities and inhibited AKT activation; and e) decreased the nuclear translocation of NF-κB. However, GANT-61 exerted these effects more effectively than GDC-0449. The in vivo antitumor activities of GDC-0449 and GANT- 61 were analyzed in BALB/c mice that were subcutaneously inoculated with mouse breast cancer (TUBO) cells. GDC-0449 and GANT-61 suppressed tumor growth of TUBO cells in BALB/c mice to different extents. These findings suggest that targeting the Hh pathway using antagonists that act downstream of SMO is a more efficient strategy than using antagonists that act upstream of SMO for interrupting Hh signaling in breast cancer

Surfactant-like Effect and Dissolution of Ultrathin Fe Films on Ag(001)

The phase immiscibility and the excellent matching between Ag(001) and Fe(001) unit cells (mismatch 0.8 %) make Fe/Ag growth attractive in the field of low dimensionality magnetic systems. Intermixing could be drastically limited at deposition temperatures as low as 140-150 K. The film structural evolution induced by post-growth annealing presents many interesting aspects involving activated atomic exchange processes and affecting magnetic properties. Previous experiments, of He and low energy ion scattering on films deposited at 150 K, indicated the formation of a segregated Ag layer upon annealing at 550 K. Higher temperatures led to the embedding of Fe into the Ag matrix. In those experiments, information on sub-surface layers was attained by techniques mainly sensitive to the topmost layer. Here, systematic PED measurements, providing chemical selectivity and structural information for a depth of several layers, have been accompanied with a few XRD rod scans, yielding a better sensitivity to the buried interface and to the film long range order. The results of this paper allow a comparison with recent models enlightening the dissolution paths of an ultra thin metal film into a different metal, when both subsurface migration of the deposit and phase separation between substrate and deposit are favoured. The occurrence of a surfactant-like stage, in which a single layer of Ag covers the Fe film is demonstrated for films of 4-6 ML heated at 500-550 K. Evidence of a stage characterized by the formation of two Ag capping layers is also reported. As the annealing temperature was increased beyond 700 K, the surface layers closely resembled the structure of bare Ag(001) with the residual presence of subsurface Fe aggregates.Comment: 4 pages, 3 figure