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

Collective decoherence of cold atoms coupled to a Bose-Einstein condensate

We examine the time evolution of cold atoms (impurities) interacting with an environment consisting of a degenerate bosonic quantum gas. The impurity atoms differ from the environment atoms, being of a different species. This allows one to superimpose two independent trapping potentials, each being effective only on one atomic kind, while transparent to the other. When the environment is homogeneous and the impurities are confined in a potential consisting of a set of double wells, the system can be described in terms of an effective spin-boson model, where the occupation of the left or right well of each site represents the two (pseudo)-spin states. The irreversible dynamics of such system is here studied exactly, i.e., not in terms of a Markovian master equation. The dynamics of one and two impurities is remarkably different in respect of the standard decoherence of the spin - boson system. In particular we show: i) the appearance of coherence oscillations, i) the presence of super and sub decoherent states which differ from the standard ones of the spin boson model, and iii) the persistence of coherence in the system at long times. We show that this behaviour is due to the fact that the pseudospins have an internal spatial structure. We argue that collective decoherence also prompts information about the correlation length of the environment. In a one dimensional configuration one can change even stronger the qualitative behaviour of the dephasing just by tuning the interaction of the bath.Comment: 18 pages, 6 figures, two references adde

Casimir-Polder interatomic potential between two atoms at finite temperature and in the presence of boundary conditions

We evaluate the Casimir-Polder potential between two atoms in the presence of an infinite perfectly conducting plate and at nonzero temperature. In order to calculate the potential, we use a method based on equal-time spatial correlations of the electric field, already used to evaluate the effect of boundary conditions on interatomic potentials. This method gives also a transparent physical picture of the role of a finite temperature and boundary conditions on the Casimir-Polder potential. We obtain an analytical expression of the potential both in the near and far zones, and consider several limiting cases of interest, according to the values of the parameters involved, such as atom-atom distance, atoms-wall distance and temperature.Comment: 11 page

Casimir-Polder potentials as entanglement probe

We have considered the interaction of a pair of spatially separated two-level atoms with the electromagnetic field in its vacuum state and we have analyzed the amount of entanglement induced between the two atoms by the non local field fluctuations. This has allowed us to characterize the quantum nature of the non local correlations of the electromagnetic field vacuum state as well as to link the induced quantum entanglement with Casimir-Polder potentials.Comment: Published on Europhysics Letters 78 (2007) 3000

Spatial correlations of vacuum fluctuations and the Casimir-Polder potential

We calculate the Casimir-Polder intermolecular potential using an effective Hamiltonian recently introduced. We show that the potential can be expressed in terms of the dynamical polarizabilities of the two atoms and the equal-time spatial correlation of the electric field in the vacuum state. This gives support to an interesting physical model recently proposed in the literature, where the potential is obtained from the classical interaction between the instantaneous atomic dipoles induced and correlated by the vacuum fluctuations. Also, the results obtained suggest a more general validity of this intuitive model, for example when external boundaries or thermal fields are present.Comment: 7 page

Theoretical analysis of the implementation of a quantum phase gate with neutral atoms on atom chips

We present a detailed, realistic analysis of the implementation of a proposal for a quantum phase gate based on atomic vibrational states, specializing it to neutral rubidium atoms on atom chips. We show how to create a double--well potential with static currents on the atom chips, using for all relevant parameters values that are achieved with present technology. The potential barrier between the two wells can be modified by varying the currents in order to realize a quantum phase gate for qubit states encoded in the atomic external degree of freedom. The gate performance is analyzed through numerical simulations; the operation time is ~10 ms with a performance fidelity above 99.9%. For storage of the state between the operations the qubit state can be transferred efficiently via Raman transitions to two hyperfine states, where its decoherence is strongly inhibited. In addition we discuss the limits imposed by the proximity of the surface to the gate fidelity.Comment: 9 pages, 5 color figure

Ire1 alpha/xbp1 axis sustains primary effusion lymphoma cell survival by promoting cytokine release and stat3 activation

Primary Effusion Lymphoma (PEL) is a highly aggressive B cell lymphoma associated with Kaposi’s Sarcoma-associated Herpesvirus (KSHV). It is characterized by a high level of basal Endoplasmic Reticulum (ER) stress, Unfolded Protein Response (UPR) activation and constitutive phosphorylation of oncogenic pathways such as the Signal Transducer and activator of Transcription (STAT3). In this study, we found that the inositol requiring kinase (IRE) 1alpha/X-box binding protein (XBP1) axis of UPR plays a key role in the survival of PEL cells, while double stranded RNA-activated protein kinase-like ER kinase (PERK) and activating transcription factor (ATF) 6 slightly influence it, in correlation with the capacity of the IRE1alpha/XBP1 axis to induce the release of interleukin (IL)-6, IL-10 and Vascular-Endothelial Growth Factor (VEGF). Moreover, we found that IRE1alpha/XBP1 inhibition reduced STAT3 Tyr705 phosphorylation and induced a pro-survival autophagy in PEL cells. In conclusion, this study suggests that targeting the IRE1alpha/XBP1 axis represents a promising strategy against PEL cells and that the cytotoxic effect of this treatment may be potentiated by autophagy inhibition

Viral Infection and Autophagy Dysregulation. The Case of HHV-6, EBV and KSHV

Human Herpes Virus-6 (HHV-6), Epstein-Barr Virus (EBV) and Kaposi Sarcoma Herpes Virus (KSHV) are viruses that share with other member of the Herpesvirus family the capacity to interfere with the autophagic process. In this paper, mainly based on the findings of our laboratory, we describe how, through different mechanisms, these viruses converge in reducing autophagy to impair DC immune function and how, by infecting and dysregulating autophagy in different cell types, they promote the pathologies associated with their infection, from the neurodegenerative diseases such Alzheimer's disease to cancer

STAT3 and mutp53 Engage a Positive Feedback Loop Involving HSP90 and the Mevalonate Pathway

Oncosuppressor TP53 and oncogene STAT3 have been shown to engage an interplay in which they negatively influence each other. Conversely, mutant (mut) p53 may sustain STAT3 phosphorylation by displacing SH2 phosphatase while whether STAT3 could influence mutp53 has not been clarified yet. In this study we found that pharmacologic or genetic inhibition of STAT3 in both glioblastoma and pancreatic cancer cells, carrying mutp53 protein, reduced mutp53 expression level by down-regulating chaperone HSP90 as well as molecules belonging to the mevalonate pathway. On the other hand, HSP90 and the mevalonate pathway were involved in sustaining STAT3 phosphorylation mediated by mutp53. In conclusion, this study unveils for the first time that mutp53 can establish with STAT3, similarly to what observed with other oncogenic pathways, a criminal alliance with a crucial role in promoting cancerogenesis

Nonlocal field correlations and dynamical Casimir-Polder forces between one excited- and two ground-state atoms

The problem of nonlocality in the dynamical three-body Casimir-Polder interaction between an initially excited and two ground-state atoms is considered. It is shown that the nonlocal spatial correlations of the field emitted by the excited atom during the initial part of its spontaneous decay may become manifest in the three-body interaction. The observability of this new phenomenon is discussed.Comment: 17 pages, 1 figure, sub. to Phys. Rev.