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Katlama C.,University Pierre and Marie Curie | Deeks S.G.,University of California at San Francisco | Autran B.,University Pierre and Marie Curie | Martinez-Picado J.,Autonomous University of Barcelona | And 8 more authors.
The Lancet | Year: 2013

Antiretroviral therapy for HIV infection needs lifelong access and strict adherence to regimens that are both expensive and associated with toxic effects. A curative intervention will be needed to fully stop the epidemic. The failure to eradicate HIV infection during long-term antiretroviral therapy shows the intrinsic stability of the viral genome in latently infected CD4T cells and other cells, and possibly a sustained low-level viral replication. Heterogeneity in latently infected cell populations and homoeostatic proliferation of infected cells might affect the dynamics of virus production and persistence. Despite potent antiretroviral therapy, chronic immune activation, inflammation, and immune dysfunction persist, and are likely to have important effects on the size and distribution of the viral reservoir. The inability of the immune system to recognise cells harbouring latent virus and to eliminate cells actively producing virus is the biggest challenge to finding a cure. We look at new approaches to unravelling the complex virus-host interactions that lead to persistent infection and latency, and discuss the rationale for combination of novel treatment strategies with available antiretroviral treatment options to cure HIV. Copyright © 2013 Elsevier B.V. Source


Ricci-Vitiani L.,Superior Health Institute | Mollinari C.,Superior Health Institute | Mollinari C.,National Research Council Italy | Biffoni M.,Superior Health Institute | De Maria R.,Superior Health Institute
Cancer | Year: 2011

BACKGROUND: Experimental data suggest that glioblastoma cells expressing the stem cell marker CD133 play a major role in radiochemoresistance and tumor aggressiveness. To date, however, there is no clinical evidence that the fraction of CD133-positive cells in glioblastoma that recurs after radiochemotherapy may be relevant for prognosis. METHODS: The authors used immunohistochemistry to assess CD133 expression in 37 paired glioblastoma samples, including 1 primary tumor sample and 1 recurrent tumor sample, after patients received adjuvant radiochemotherapy. To assess the actual composition of the CD133-positive glioblastoma cell population, fluorescence-associated cell sorting (FACS) analysis was used to sort CD133-positive/CD45-negative cells that were assayed for tumor-specific chromosomal aberrations using interphase fluorescence in situ hybridization. To rule out endothelial precursor cells, CD133-positive fractions also were assayed with anti-CD34 by FACS. RESULTS: In recurrent glioblastomas, the percentage of CD133-positive cells was increased by 4.6-fold compared with the percentage in primary glioblastomas, although, in some tumors, it increased up to 10-fold and 20-fold. Unexpectedly, the increase in CD133 expression was associated significantly with longer survival after tumor recurrence. An analysis of tumor-specific chromosomal aberrations and in vivo studies revealed that the CD133-positive cell compartment of recurrent glioblastoma was composed of both cancer stem cells and nontumor neural stem cells. The latter cells represented from 20% to 60% of the CD133-positive cell population, and their relative percentage favorably affected the survival of patients with recurrent glioblastoma. Endothelial CD133-positive/CD34-positive precursors did not contribute to the CD133-positive cell population. CONCLUSIONS: The authors hypothesized that, similar to the phenomenon described in glioblastoma models, neural stem/progenitor cells that are recruited by the tumor from surrounding brain may exert an antitumorigenic effect. © 2010 American Cancer Society. Source


Tirelli V.,Superior Health Institute | Ghinassi B.,Mount Sinai School of Medicine | Migliaccio A.R.,Mount Sinai School of Medicine | Whitsett C.,Mount Sinai School of Medicine | And 3 more authors.
Stem Cells International | Year: 2011

In Human Erythroid Massive Amplification (HEMA) cultures, AB mononuclear cells (MNC) generate 1-log more erythroid cells (EBs) than the corresponding CD 34 pos cells, suggesting that MNC may also contain CD 34 neg HPC. To clarify the phenotype of AB HPC which generate EBs in these cultures, flow cytometric profiling for CD34/CD36 expression, followed by isolation and functional characterization (colony-forming-ability in semisolid-media and fold-increase in HEMA) were performed. Four populations with erythroid differentiation potential were identified: CD 34 pos CD 36 neg (0.1); CD 34 pos CD 36 pos (barely detectable-0.1); CD 34 neg CD 36 low (2) and CD 34 neg CD 36 neg (75). In semisolid-media, CD 34 pos CD 36 neg cells generated BFU-E and CFU-GM (in a 1:1 ratio), CD 34 neg CD 36 neg cells mostly BFU-E (87) and CD 34 pos CD 36 pos and CD 34 neg CD 36 low cells were not tested due to low numbers. Under HEMA conditions, CD 34 pos CD 36 neg, CD 34 pos CD 36 pos, CD 34 neg CD 36 low and CD 34 neg CD 36 neg cells generated EBs with fold-increases of 9,000, 100, 60 and 1, respectively, and maturation times (day with >10 C D 36 h i g h C D 235 a h i g h cells) of 107 days. Pyrenocytes were generated only by CD 34 neg / CD 36 neg cells by day 15. These results confirm that the majority of HPC in AB express CD34 but identify additional CD 34 neg populations with erythroid differentiation potential which, based on differences in fold-increase and maturation times, may represent a hierarchy of HPC present in AB. © 2011 Valentina Tirelli et al. Source


Fabbri A.,Superior Health Institute | Travaglione S.,Superior Health Institute | Ballan G.,Superior Health Institute | Loizzo S.,Superior Health Institute | Fiorentini C.,Superior Health Institute
Toxins | Year: 2013

Certain strains of Escherichia coli have been indicated as a risk factor for colon cancer. E. coli is a normal inhabitant of the human intestine that becomes pathogenic, especially in extraintestinal sites, following the acquisition of virulence factors, including the protein toxin CNF1. This Rho GTPases-activating toxin induces dysfunctions in transformed epithelial cells, such as apoptosis counteraction, pro-inflammatory cytokines' release, COX2 expression, NF-kB activation and boosted cellular motility. As cancer may arise when the same regulatory pathways are affected, it is conceivable to hypothesize that CNF1-producing E. coli infections can contribute to cancer development. This review focuses on those aspects of CNF1 related to transformation, with the aim of contributing to the identification of a new possible carcinogenic agent from the microbial world. © 2013 by the authors; licensee MDPI, Basel, Switzerland. Source


Travaglione S.,Superior Health Institute | Loizzo S.,Superior Health Institute | Ballan G.,Superior Health Institute | Fiorentini C.,Superior Health Institute | Fabbri A.,Superior Health Institute
Toxins | Year: 2013

The Cytotoxic Necrotizing Factor 1 (CNF1), a protein toxin from pathogenic E. coli, modulates the Rho GTPases, thus, directing the organization of the actin cytoskeleton. In the nervous system, the Rho GTPases play a key role in several processes, controlling the morphogenesis of dendritic spines and synaptic plasticity in brain tissues. This review is focused on the peculiar property of CNF1 to enhance brain plasticity in in vivo animal models of central nervous system (CNS) diseases, and on its possible application in therapy. © 2014 by the authors; licensee MDPI, Basel, Switzerland. Source

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