Sensitization of cervix cancer cells to Adriamycin by Pentoxifylline induces an increase in apoptosis and decrease senescence

<p>Abstract</p> <p>Background</p> <p>Chemotherapeutic drugs like Adriamycin (ADR) induces apoptosis or senescence in cancer cells but these cells often develop resistance and generate responses of short duration or complete failure. The methylxantine drug Pentoxifylline (PTX) used routinely in the clinics setting for circulatory diseases has been recently described to have antitumor properties. We evaluated whether pretreatment with PTX modifies apoptosis and senescence induced by ADR in cervix cancer cells.</p> <p>Methods</p> <p>HeLa (HPV 18+), SiHa (HPV 16+) cervix cancer cells and non-tumorigenic immortalized HaCaT cells (control) were treated with PTX, ADR or PTX + ADR. The cellular toxicity of PTX and survival fraction were determinated by WST-1 and clonogenic assay respectively. Apoptosis, caspase activation and ADR efflux rate were measured by flow cytometry, senescence by microscopy. IκBα and DNA fragmentation were determinated by ELISA. Proapoptotic, antiapoptotic and senescence genes, as well as HPV-E6/E7 mRNA expression, were detected by time real RT-PCR. p53 protein levels were assayed by Western blot.</p> <p>Results</p> <p>PTX is toxic (WST-1), affects survival (clonogenic assay) and induces apoptosis in cervix cancer cells. Additionally, the combination of this drug with ADR diminished the survival fraction and significantly increased apoptosis of HeLa and SiHa cervix cancer cells. Treatments were less effective in HaCaT cells. We found caspase participation in the induction of apoptosis by PTX, ADR or its combination. Surprisingly, in spite of the antitumor activity displayed by PTX, our results indicate that methylxantine, <it>per se </it>does not induce senescence; however it inhibits senescence induced by ADR and at the same time increases apoptosis. PTX elevates IκBα levels. Such sensitization is achieved through the up-regulation of proapoptotic factors such as <it>caspase </it>and <it>bcl </it>family gene expression. PTX and PTX + ADR also decrease E6 and E7 expression in SiHa cells, but not in HeLa cells. p53 was detected only in SiHa cells treated with ADR.</p> <p>Conclusion</p> <p>PTX is a good inducer of apoptosis but does not induce senescence. Furthermore, PTX reduced the ADR-induced senescence and increased apoptosis in cervix cancer cells.</p

Milagro limits and HAWC sensitivity for the rate-density of evaporating Primordial Black Holes

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On the sensitivity of the HAWC observatory to gamma-ray bursts

We present the sensitivity of HAWC to Gamma Ray Bursts (GRBs). HAWC is a very high-energy gamma-ray observatory currently under construction in Mexico at an altitude of 4100 m. It will observe atmospheric air showers via the water Cherenkov method. HAWC will consist of 300 large water tanks instrumented with 4 photomultipliers each. HAWC has two data acquisition (DAQ) systems. The main DAQ system reads out coincident signals in the tanks and reconstructs the direction and energy of individual atmospheric showers. The scaler DAQ counts the hits in each photomultiplier tube (PMT) in the detector and searches for a statistical excess over the noise of all PMTs. We show that HAWC has a realistic opportunity to observe the high-energy power law components of GRBs that extend at least up to 30 GeV, as it has been observed by Fermi LAT. The two DAQ systems have an energy threshold that is low enough to observe events similar to GRB 090510 and GRB 090902b with the characteristics observed by Fermi LAT. HAWC will provide information about the high-energy spectra of GRBs which in turn could help to understanding about e-pair attenuation in GRB jets, extragalactic background light absorption, as well as establishing the highest energy to which GRBs accelerate particles

Discovery of a multiply lensed submillimeter galaxy in early HerMES Herschel/SPIRE data

‘In these times, during the rise in the popularity of institutional repositories, the Society does not forbid authors from depositing their work in such repositories. However, the AAS regards the deposit of scholarly work in such repositories to be a decision of the individual scholar, as long as the individual's actions respect the diligence of the journals and their reviewers.’ Original article can be found at: http://iopscience.iop.org/ Copyright American Astronomical SocietyWe report the discovery of a bright (f (250 μm)>400 mJy), multiply lensed submillimeter galaxy HERMES J105751.1+573027 in Herschel/SPIRE Science Demonstration Phase data from the HerMES project. Interferometric 880 μm Submillimeter Array observations resolve at least four images with a large separation of ∼9″. A high-resolution adaptive optics Kp image with Keck/NIRC2 clearly shows strong lensing arcs. Follow-up spectroscopy gives a redshift of z = 2.9575, and the lensing model gives a total magnification of μ ∼ 11 ± 1. The large image separation allows us to study the multi-wavelength spectral energy distribution (SED) of the lensed source unobscured by the central lensing mass. The far-IR/millimeter-wave SED is well described by a modified blackbody fit with an unusually warm dust temperature, 88 ± 3 K. We derive a lensing-corrected total IR luminosity of (1.43 ± 0.09) × 1013 L⊙, implying a star formation rate of ∼2500 M⊙ yr-1. However, models primarily developed from brighter galaxies selected at longer wavelengths are a poor fit to the full optical-to-millimeter SED. A number of other strongly lensed systems have already been discovered in early Herschel data, and many more are expected as additional data are collected.Peer reviewe