The scalar glueball spectrum

We discuss scenarios for scalar glueballs using arguments based on sum rules, spectral decomposition, the $\frac{1}{N_c}$ approximation, the scales of the strong interaction and the topology of the flux tubes. We analyze the phenomenological support of those scenarios and their observational implications. Our investigations hint a rich low lying glueball spectrum.Comment: 11 pages: New title, figure, table and a more detailed comparison with experiment

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

SAHA, an inhibitor of histone deacetylase activity, has been shown to sensitize tumor cells to apoptosis induced by TRAIL, a member of TNF-family. In this paper we investigated the effect of SAHA/TRAIL combination in two breast cancer cell lines, the ERa positive MCF-7 and the ERa negative MDA-MB231. Treatment of MDA-MB231 and MCF-7 cells with SAHA in combination with TRAIL caused detachment of cells followed by anoikis, a form of apoptosis which occurs after cell detachment, while treatment with SAHA or TRAIL alone did not produce these effects. The effects were more evident in MDA-MB231 cells, which were chosen for ascertaining the mechanism of SAHA/TRAIL action. Our results show that SAHA decreased the level of c-FLIP, thus favouring the interaction of TRAIL with the specific death receptors DR4 and DR5 and the consequent activation of caspase-8. These effects increased when the cells were treated with SAHA/TRAIL combination. Because z-IEDT-fmk, an inhibitor of caspase-8, prevented both the cleavage of the focal adhesion-kinase FAK and cell detachment, we suggest that activation of caspase- 8 can be responsible for both the decrement of FAK and the consequent cell detachment. In addition, treatment with SAHA/TRAIL combination caused dissipation of DJm, activation of caspase-3 and decrement of both phospho-EGFR and phospho-ERK1/2, a kinase which is involved in the phosphorylation of BimEL. Therefore, co-treatment also induced decrement of phospho-BimEL and a concomitant increase in the dephosphorylated form of BimEL, which plays an important role in the induction of anoikis. Our findings suggest the potential application of SAHA in combination with TRAIL in clinical trials for breast cancer

A short story of 3AB-OS cancer stem cells, a possible model for studying cancer stemness

Cancer Stem Cells (CSCs) are thought to be the cause of cancer initiation, growth and development. Thus, a challenge in cancer research is their identification and eradication. In our laboratory, by chemical treatment of the human osteosarcoma (OS) MG63 cell line, we have isolated and characterized 3AB-OS cells, a human OS CSC line. 3AB-OS cells transdifferentiate in vitro into cells of the three derivatives germ layers and, when xenografted in athymic mice they are highly tumorigenic and recapitulate in vivo crucial features of human OS. They even express a reprogrammed energy metabolism, with a dependence on glycolytic metabolism more strong than parental MG63 cells. 3AB-OS cells have chromosomes showing a great number of abnormalities which are very similar to abnormalities found in both pediatric and adult osteosarcomas. In comparison with parental MG63 cells (where TP53 gene is hypermethylated, rearranged and in single copy), 3AB-OS cells have TP53 gene unmethylated, rearranged and in multiple copies. Moreover, the mutp53 (p53-R248W/P72R) is post-translationally stabilized, has nuclear localization and a gain of function. A great number of results obtained in our laboratories suggested that p53 mutation could be the “driver mutation” at the origin of the transformation of MG63 cells into 3AB-OS CSCs

Parthenolide induces caspase-independent cell death in osteosarcoma, melanoma and breast cancer cells through the induction of oxidative stress.

Parthenolide, a sesquiterpene lactone found in European feverfew, is used in traditional medicine for its anti-inflammatory activity. In addition, parthenolide has been considered as a novel and effective anti-tumor agent because it induces cytotoxic effects in several tumor cell lines. Our studies demonstrated that parthenolide exerted strong cytotoxic effects in osteosarcoma MG63 and melanoma SK-Mel28 cells in culture. Staining with Hoechst 33342 revealed in most cells after brief periods of treatments (3-5h) chromatin condensation and fragmentation, while only few cells were PI-positive. Prolonging the treatment (5-14h) PI-positive cells strongly augmented, denouncing the increase of necrotic effects. All these effects were prevented by NAC, while caspase inhibitors were ineffective, thus suggesting a caspase-independent cell death. The study of the mechanism of action provided evidence that treatment with parthenolide rapidly stimulated (1-2 h) ROS generation, in particular by inducing activation of extracellular signal-regulated kinase1/2 and NADPH oxidase. This event caused depletion of thiol groups and glutathione, NF-\u3baB inhibition, JNK activation and cell detachment from the matrix. ROS generation together with mitochondrial accumulation of Ca2+ favoured dissipation of \u394\u3c8m, which appeared primarily determined by the opening of the permeability transition pore (PTP), since \u394\u3c8m loss was partially prevented by cyclosporin A, an inhibitor of PTP opening. Recently, we focused our attention on MDA-MB231 cells, a very aggressive and poorly differentiated breast cancer cell line, which is negative for estrogen receptor alpha. Preliminary results suggested that parthenolide induced cell death in these cells with a mechanism similar to that demonstrated in osteosarcoma and melanoma cells. Interestingly, we demonstrated that in MDA-MB231 cells the effect of parthenolide was potentiated by the addition of z-VAD-fmk, a general inhibitor of caspases. Studies are in progress to elucidate the mechanism of this interaction which could suggest new strategies for the treatment of ER-\u3b1 negative breast cancer

Hadron Correlators and the Structure of the Quark Propagator

The structure of the quark propagator of $QCD$ in a confining background is not known. We make an Ansatz for it, as hinted by a particular mechanism for confinement, and analyze its implications in the meson and baryon correlators. We connect the various terms in the K\"allen-Lehmann representation of the quark propagator with appropriate combinations of hadron correlators, which may ultimately be calculated in lattice $QCD$. Furthermore, using the positivity of the path integral measure for vector like theories, we reanalyze some mass inequalities in our formalism. A curiosity of the analysis is that, the exotic components of the propagator (axial and tensor), produce terms in the hadron correlators which, if not vanishing in the gauge field integration, lead to violations of fundamental symmetries. The non observation of these violations implies restrictions in the space-time structure of the contributing gauge field configurations. In this way, lattice $QCD$ can help us analyze the microscopic structure of the mechanisms for confinement.Comment: 12 pp in LaTeX, preprint Univ. of Valencia, FTUV/94-16, IFIC/94-15. To appear in Z.Phys.

Relativity and constituent quark structure in model calculations of parton distributions

According to recent studies, Parton Distribution Functions (PDFs) and Generalized Parton Distributions (GPDs) can be evaluated in a Constituent Quark Model (CQM) scenario, considering the constituent quarks as composite objects. In here, a fully covariant model for a system of two particles, together with its non relativistic limit, are used to calculate PDFs and GPDs. The analysis permits to realize that by no means the effects of Relativity can be simulated taking into account the structure of the constituent particles, the two effects being independent and necessary for a proper description of available high energy data in terms of CQM

VUV and X-ray coherent light with tunable polarization from single-pass free-electron lasers

Tunable polarization over a wide spectral range is a required feature of light sources employed to investigate the properties of local symmetry in both condensed and low-density matter. Among new-generation sources, free-electron lasers possess a unique combination of very attractive features, as they allow to generate powerful and coherent ultra-short optical pulses in the VUV and X-ray spectral range. However, the question remains open about the possibility to freely vary the light polarization of a free-electron laser, when the latter is operated in the so-called nonlinear harmonic-generation regime. In such configuration, one collects the harmonics of the free-electron laser fundamental emission, gaining access to the shortest possible wavelengths the device can generate. In this letter we provide the first experimental characterization of the polarization of the harmonic light produced by a free-electron laser and we demonstrate a method to obtain tunable polarization in the VUV and X-ray spectral range. Experimental results are successfully compared to those obtained using a theoretical model based on the paraxial solution of Maxwell's equations. Our findings can be expected to have a deep impact on the design and realization of experiments requiring full control of light polarization to explore the symmetry properties of matter samples

In human retinoblastoma Y79 cells okadaic acid\u2013parthenolide co-treatment induces synergistic apoptotic effects, with PTEN as a key player.

Retinoblastoma is the most common intraocular malignancy of childhood. In developing countries, treatment is limited, long-term survival rates are low and current chemotherapy causes significant morbidity to pediatric patients and significantly limits dosing. Therefore there is an urgent need to identify new therapeutic strategies to improve the clinical outcome of patients with retinoblastoma. here, we investigated the effects of two natural compounds okadaic acid (OKa) and parthenolide (PN) on human retinoblastoma Y79 cells. For the first time we showed that OKa/PN combination at subtoxic doses induces potent synergistic apoptotic effects accompanied by lowering in p-akt levels, increasing in the stabilized forms of p53 and potent decrease in ps166-Mdm2. We also showed the key involvement of PTeN which, after OKa/PN treatment, potently increased before p53, thus suggesting that p53 activation was under PTeN action. Moreover, after PTEN-knockdown p-akt/ ps166Mdm2 increased over basal levels and p53 significantly lowered, while OKa/PN treatment failed both to lower p-akt and ps166-Mdm2 and to increase p53 below/over their basal levels respectively. OKa/PN treatment potently increased ROs levels whereas decreased those of Gsh. Reducing cellular Gsh by l-butathionine-[s,R]-sulfoximine treatment significantly anticipated the cytotoxic effect exerted by OKa/ PN. Furthermore, the effects of OKa/PN treatment on both Gsh content and cell viability were less pronounced in PTeN silenced cells than in control cells. The results provide strong suggestion for combining a treatment approach that targets the PTeN/akt/Mdm2/p53 pathway

The oxygen radicals involved in the toxicity induced by parthenolide in MDA-MB-231 cells

It has been shown that the sesquiterpene lactone parthenolide lowers the viability of MDA-MB-231 breast cancer cells, in correlation with oxidative stress. The present report examined the different radical species produced during parthenolide treatment and their possible role in the toxicity caused by the drug. Time course experiments showed that in the first phase of treatment (0-8 h), and in particular in the first 3 h, parthenolide induced dichlorofluorescein (DCF) signal in a large percentage of cells, while dihydroethidium (DHE) signal was not stimulated. Since the effect on DCF signal was suppressed by apocynin and diphenyleneiodonium (DPI), two inhibitors of NADPH oxidase (NOX), we suggest that parthenolide rapidly stimulated NOX activity with production of superoxide anion (O2•-), which was converted by superoxide dismutase 1 (SOD1) into hydrogen peroxide (H2O2). In the second phase of treatment (8-16 h), parthenolide increased the number of positive cells to DHE signal. Since this event was not prevented by apocynin and DPI and was associated with positivity of cells to MitoSox Red, a fluorochrome used to detect mitochondrial production of O2•-, we suggest that parthenolide induced production of O2•- at the mitochondrial level independently by NOX activity in the second phase of treatment. Finally, in this phase, most cells became positive to hydroxyphenyl fluorescein (HPF) signal, a fluorescent probe to detect highly reactive oxygen species (hROS), such as hydroxyl radical and peroxynitrite. Therefore, parthenolide between 8-16 h of treatment induced generation of O2•- and hROS, in close correlation with a marked reduction in cell viability

Dynamical confinement in bosonized QCD2

In the bosonized version of two dimensional theories non trivial boundary conditions (topology) play a crucial role. They are inevitable if one wants to describe non singlet states. In abelian bosonization, color is the charge of a topological current in terms of a non-linear meson field. We show that confinement appears as the dynamical collapse of the topology associated with its non trivial boundary conditions.Comment: 11 pages, figures not included, ftuv/92-