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

Abstract

The High Altitude Water Cherenkov (HAWC) observatory is an array of large water Cherenkov detectors sensitive to gamma rays and hadronic cosmic rays in the energy band between 100 GeV and 100 TeV. The observatory will be used to measure high-energy protons and cosmic rays via detection of the energetic secondary particles reaching the ground when one of these particles interacts in the atmosphere above the detector. HAWC is under construction at a site 4100 meters above sea level on the northern slope of the volcano Sierra Negra, which is located in central Mexico at 19 N latitude. It is scheduled for completion in 2014. In this paper we estimate the sensitivity of the HAWC instrument to point-like and extended sources of gamma rays. The source fluxes are modeled using both unbroken power laws and power laws with exponential cutoffs. HAWC, in one year, is sensitive to point sources with integral power-law spectra as low as 5 10-13 cm-2sec-1 above 2 TeV (approximately 50 mCrab) over 5 sr of the sky. This is a conservative estimate based on simple event parameters and is expected to improve as the data analysis techniques are refined. We discuss known TeV sources and the scientific contributions that HAWC can make to our understanding of particle acceleration in these sources. " 2013 Elsevier B.V. All rights reserved.",,,,,,"10.1016/j.astropartphys.2013.08.002",,,"http://hdl.handle.net/20.500.12104/44464","http://www.scopus.com/inward/record.url?eid=2-s2.0-84887431030&partnerID=40&md5=b5d93bb6025b6d29331e2f6d3809a1ff",,,,,,,,"Astroparticle Physics",,"26

32",,"50-52",,"Scopus

WOS",,,,,,"Cosmic ray; TeV gamma-ray astronomy; Water cherenkov",,,,,,"Sensitivity of the high altitude water Cherenkov detector to sources of multi-TeV gamma rays",,"Article" "46236","123456789/35008",,"Jay, O., Centro de Estudios de Especies Menores, Universidad de Guantánamo, Carretera al Salvador km 6 1/2, Guantánamo, Cuba; Torres, V., Instituto de Ciencia Animal, Apartado Postal 24, San-José de las Lajas, Mayabeque, Cuba; Marrero, Y., Instituto de Ciencia Animal, Apartado Postal 24, San-José de las Lajas, Mayabeque, Cuba; Torres, J.P., Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Las Agujas, Zapopan, Jalisco, Mexico",,"Jay, O.

Torres, V.

Marrero, Y.

Torres, J.P.",,"2012",,"In order to improve the ruminant feed evaluation techniques through a statistical method permitting the comparison of treatments in experiments of in vitro gas production, based on regression curves, data were collected from an experiment of in vitro gas production. The Gompertz function was fitted and the Monte Carlo simulation method was used, with the aim of analyzing the sensibility of four homogeneity tests of non-linear regression models. Thirteen new treatments were obtained, with 300 repetitions each and 280 points simulated per each repetition. The homogeneity tests were: extra sum of squares, Bayesian information criterion (BIC), Akaike information criterion (AIC), and Akaike information criterion corrected (AICC). The comparison criteria were assessed with modifications to the parameters, on the order of 1, 3, 5, and 10 %. The methodology for the comparison of the curves was based on the definition of the complete and the reduced models. The sensibility of each method was established according to the probability of fulfillment of the null hypothesis. The AICC showed higher sensibility, followed by the test of extra sum of squares. The AIC and the BIC were the least sensible. The parameter that affected the most the differences between treatments was the asymptotic coefficient (A).",,,,,,,,,"http://hdl.handle.net/20.500.12104/44457","http://www.scopus.com/inward/record.url?eid=2-s2.0-84879814468&partnerID=40&md5=361ce1a7ba1563364699cccfc8ffa32e",,,,,,"1",,"Cuban Journal of Agricultural Science",,"15

22",,"46",,"Scopus",,,,,,"Comparison of treatments; Extra sum of squares; Information criterion; Non-linear regression",,,,,,"Sensibility analysis of homogeneity tests of in vitro gas production curves by Monte Carlo simulation",,"Article" "46245","123456789/35008",,"Bravo-Cuellar, A., División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada 800, Colonia Independencia. Guadalajara, Jalisco, CP 44340, Mexico, Departamento Ciencias de la Salud, Centro Universitario de los Altos, Universidad de Guadalajara, Km 7, 5 Carretera a Yahualica, Tepatitlan de Morelos, Jalisco, CP 47820, Mexico; Ortiz-Lazareno, P.C., División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada 800, Colonia Independencia. Guadalajara, Jalisco, CP 44340, Mexico; Lerma-Diaz, J.M., División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada 800, Colonia Independencia. Guadalajara, Jalisco, CP 44340, Mexico; Dominguez-Rodriguez, J.R., División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada 800, Colonia Independencia. Guadalajara, Jalisco, CP 44340, Mexico; Jave-Suarez, L.F., División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada 800, Colonia Independencia. Guadalajara, Jalisco, CP 44340, Mexico; Aguilar-Lemarroy, A., División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada 800, Colonia Independencia. Guadalajara, Jalisco, CP 44340, Mexico; del Toro-Arreola, S., Laboratorio de Inmunología, Centro Universitario Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, puerta 7, Colonia Independencia. Guadalajara, Jalisco, CP 44340, Mexico; de Celis-Carrillo, R., División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada 800, Colonia Independencia. Guadalajara, Jalisco, CP 44340, Mexico; Sahagun-Flores, J.E., Laboratorio de Inmunología, Centro Universitario Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, puerta 7, Colonia Independencia. Guadalajara, Jalisco, CP 44340, Mexico, Hospital Regional Valentín Gómez Farías, Instituto de Seguridad Social y Servicios Sociales de los Trabajadores del Estado, Avenida Soledad Orozco 203, Colonia el Capullo, Guadalajara, Jalisco. CP 45150, Mexico; de Alba-García, J.E.G., Unidad de Investigación Social, Epidemiológica y Servicios de Salud, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Belisario Domínguez 1000, Colonia Independencia, Guadalajara, Jalisco, CP 44340, Mexico; Hernandez-Flores, G., División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada 800, Colonia Independencia. Guadalajara, Jalisco, CP 44340, Mexico",,"Bravo-Cuellar, A.

Ortiz-Lazareno, P.C.

Lerma-Diaz, J.M.

Dominguez-Rodriguez, J.R.

Jave-Suarez, L.F.

Aguilar-Lemarroy, A.

del Toro-Arreola, S.

de Celis-Carrillo, R.

Sahagun-Flores, J.E.

de Alba-García, J.E.G.

Hernandez-Flores, G.",,"2010",,"Background: 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.Methods: 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. I?B? 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.Results: 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, per se does not induce senescence; however it inhibits senescence induced by ADR and at the same time increases apoptosis. PTX elevates I?B? levels. Such sensitization is achieved through the up-regulation of proapoptotic factors such as caspase and bcl 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.Conclusion: 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. " 2010 Bravo-Cuellar et al; licensee BioMed Central Ltd.