In silico analysis of the binding properties of solasonine to mortalin and p53, and in vitro pharmacological studies of its apoptotic and cytotoxic effects on human HepG2 and Hep3b hepatocellular carcinoma cells.

Liver cancer, of which human hepatocellular carcinoma (HCC) is the most common type, represents the second most common cause of death from cancer worldwide. To date, treatments remain mostly ineffective and efforts are made to discover new molecules or therapeutic strategies against HCC. Mortalin, an hsp70 chaperone protein, is overexpressed in various cancer, including HCC.

Cytotoxic, apoptotic, and sensitization properties of ent-kaurane-type diterpenoids from Croton tonkinensis Gagnep on human liver cancer HepG2 and Hep3b cell lines.

Human hepatocellular carcinoma (HCC) is the most common type of liver cancer, the second most common cause of death from cancer worldwide. A very poor prognosis and a lack of effective treatments make liver cancer a major public health problem, notably in less developed regions, particularly in eastern Asia. This fully justifies the search of new molecules and therapeutic strategies against HCC.

Application of "taxocene surrogation" and "taxonomic sufficiency" concepts to fish farming environmental monitoring. Comparison of BOPA index versus polychaete assemblage structure.

"Taxocene surrogation" and "taxonomic sufficiency" concepts were applied to the monitoring of soft bottoms macrobenthic assemblages influenced by fish farming following two approaches. Polychaete assemblage evaluation through multivariate analysis and the benthic index BOPA were compared. Six fish farms along the Spanish Mediterranean coast were monitored.

A meta-analysis approach to the effects of fish farming on soft bottom polychaeta assemblages in temperate regions.

Marine fish farms could cause environmental disturbances on the sediment due to uneaten food and fish faeces that impact the marine benthos. Polychaete assemblages are considered good indicators of environmental perturbations. The present study aimed to establish groups of polychaetes as potential indicators of fish farm pollution.

Melanoma chemotherapy leads to the selection of ABCB5-expressing cells.

Metastatic melanoma is the most aggressive skin cancer. Recently, phenotypically distinct subpopulations of tumor cells were identified. Among them, ABCB5-expressing cells were proposed to display an enhanced tumorigenicity with stem cell-like properties.

Concepts and ways to amplify the antitumor immune response.

In this chapter, a detailed description of how the innate and adaptive immune responses interact with malignant cells is presented. In addition, we discuss how developing tumors establish themselves, and how they benefit on one hand and organize their defense against the immune system on the other hand. New data from three tumor model systems in mice are discussed; in particular, the intricate interactions between the immune cells and the tumor cells are highlighted.

In vivo major histocompatibility complex class I (MHCI) expression on MHCIlow tumor cells is regulated by gammadelta T and NK cells during the early steps of tumor growth.

Cell surface expression of MHC class I molecules by tumor cells is determinant in the interplay between tumor cells and the immune system. Nevertheless, the mechanisms which regulate MHCI expression on tumor cells are not clear. We previously showed that immune innate cells from the spleen can regulate MHCI expression on MHCI(low) tumor cells.

Pharmacological screening of bryophyte extracts that inhibit growth and induce abnormal phenotypes in human HeLa cancer cells.

Antitumor activities of substances from natural sources apart from vascular plants and micro-organisms have been poorly investigated. Here we report on a pharmacological screening of a bryophyte extract library using a phenotypic cell-based assay revealing microtubules, centrosomes and DNA. Among the 219 moss extracts tested, we identified 41 extracts acting on cell division with various combinations of significant effects on interphasic and mitotic cells.

Characterization and differential expression of a newly identified phosphorylated isoform of the human 20S proteasome beta7 subunit in tumor vs. normal cell lines.

The search of new pharmacological targets with original mechanism of action within the ubiquitin-proteasome pathway is still a goal to be reached in oncopharmacology. Modification by phosphorylation/dephosphorylation has been found to be involved in cancer and to regulate functional activity of proteasome. Until now, phosphorylated forms of alpha subunits of the 20S human proteasome have been mostly reported.

[Bryophytes, a potent source of drugs for tomorrow's medicine?].

Although secondary plant metabolites provided numerous leads for the development of a wide array of therapeutic drugs, the discovery of new drugs with novel structures has declined in the past few years. Indeed higher plants have a similar evolutionary history and so produce similar metabolites. Search for novel sources of new therapeutic compounds within unexplored parts of biodiversity is thus an attractive challenge.

The innate immune system recognizes and regulates major histocompatibility complex class I (MHCI) expression on MHCIlow tumor cells.

Tumor cells and the immune system play a lethal "pas de deux" during tumor development. However, it is not clear which role the innate immune system plays in these interactions. We studied the interaction of normal spleen cells (NSCs) with tumor cells expressing low levels of MHCI on the cell surface.

Inhibition of proteasome activity impairs centrosome-dependent microtubule nucleation and organization.

Centrosomes are dynamic organelles that consist of a pair of cylindrical centrioles, surrounded by pericentriolar material. The pericentriolar material contains factors that are involved in microtubule nucleation and organization, and its recruitment varies during the cell cycle. We report here that proteasome inhibition in HeLa cells induces the accumulation of several proteins at the pericentriolar material, including gamma-tubulin, GCP4, NEDD1, ninein, pericentrin, dynactin, and PCM-1.

Capture of membrane components via trogocytosis occurs in vivo during both dendritic cells and target cells encounter by CD8(+) T cells.

Cytotoxic T lymphocytes recently stimulated by antigen-presenting cells (APC) display major histocompatibility class (MHC) I and II molecules inherited from APC. We have previously reported that, in vitro, transfer of MHC molecules and several other proteins occurs through trogocytosis, i.e.

Allosteric changes in the TCR/CD3 structure upon interaction with extra- or intra-cellular ligands.

T lymphocytes are activated by the interaction between the T-cell antigen receptor (TCR) and peptides presented by major histocompatibility complex (MHC) molecules. The avidity of this TCR-pMHC interaction is very low. Therefore, several hypotheses have been put forward to explain how T cells become specifically activated despite this handicap: conformational change model, aggregation model, kinetic segregation model, sequential interaction model and permissive geometry model.

Interactions between CD8alphabeta and the TCRalphabeta/CD3-receptor complex.

CD8+ T cells recognize antigenic peptides bound to major histocompatibility complex (MHC) class I molecules on normal antigen-presenting cells (APC), as well as on virus-infected cells or tumour cells (pMHC). At least two receptor types participate in recognition of these complexes: T-cell receptor (TCR) alphabeta heterodimers and CD8alphabeta molecules. The former molecules react with antigenic peptide and variable regions of MHC class I molecules, whereas the latter molecules react with constant alpha3 regions of MHC class I molecules.

The use of mass spectrometry to identify antigens from proteasome processing.

Mass spectrometry (MS) is a powerful tool for the characterization of antigenic peptides that play a major role in the immune system. Most of the major histocompatibility complex (MHC) class I peptides are generated during the degradation of intracellular proteins by the proteasome, a catalytic complex present in all eukaryotic cells. This chapter focuses on the contribution of MS to the understanding of the mechanisms of antigen processing by the proteasome.

Destructive cleavage of antigenic peptides either by the immunoproteasome or by the standard proteasome results in differential antigen presentation.

The immunoproteasome (IP) is usually viewed as favoring the production of antigenic peptides presented by MHC class I molecules, mainly because of its higher cleavage activity after hydrophobic residues, referred to as the chymotrypsin-like activity. However, some peptides have been found to be better produced by the standard proteasome. The mechanism of this differential processing has not been described.

Effect of ajoene, a natural antitumor small molecule, on human 20S proteasome activity in vitro and in human leukemic HL60 cells.

The pharmacologic properties of ajoene, the major sulfur-containing compound purified from garlic, and its possible role in the prevention and treatment of cancer has received increasing attention. Several studies demonstrated that induction of apoptosis and cell cycle blockade are typical biologic effects observed in tumor cells after proteasome inhibition. The proteasome is responsible for the degradation of a variety of intracellular proteins and plays a key role in the regulation of many cellular processes.

Characterization of protein variants and post-translational modifications: ESI-MSn analyses of intact proteins eluted from polyacrylamide gels.

We have developed a strategy to characterize protein isoforms, resulting from single-point mutations and post-translational modifications. This strategy is based on polyacrylamide gel electrophoresis separation of protein isoforms, mass spectrometry (MS) and MSn analyses of intact proteins, and tandem MS analyses of proteolytic peptides. We extracted protein isoforms from polyacrylamide gels by passive elution using SDS, followed by nanoscale hydrophilic phase chromatography for SDS removal.

T cells infiltrate the brain in murine and human transmissible spongiform encephalopathies.

CD4 and CD8 T lymphocytes infiltrate the parenchyma of mouse brains several weeks after intracerebral, intraperitoneal, or oral inoculation with the Chandler strain of mouse scrapie, a pattern not seen with inoculation of prion protein knockout (PrP(-/-)) mice. Associated with this cellular infiltration are expression of MHC class I and II molecules and elevation in levels of the T-cell chemokines, especially macrophage inflammatory protein 1beta, IFN-gamma-inducible protein 10, and RANTES. T cells were also found in the central nervous system (CNS) in five of six patients with Creutzfeldt-Jakob disease.

A new generation of Melan-A/MART-1 peptides that fulfill both increased immunogenicity and high resistance to biodegradation: implication for molecular anti-melanoma immunotherapy.

Intense efforts of research are made for developing antitumor vaccines that stimulate T cell-mediated immunity. Tumor cells specifically express at their surfaces antigenic peptides presented by MHC class I and recognized by CTL. Tumor antigenic peptides hold promise for the development of novel cancer immunotherapies.

Pleiotropic effects of post-translational modifications on the fate of viral glycopeptides as cytotoxic T cell epitopes.

The fate of viral glycopeptides as cytotoxic T lymphocyte (CTL) epitopes is unclear. We have dissected the mechanisms of antigen presentation and CTL recognition of the peptide GP392-400 (WLVTNGSYL) from the lymphocytic choriomeningitis virus (LCMV) and compared them with those of the previously reported GP92-101 antigen (CSANNSHHYI). Both GP392-400 and GP92-101 bear a glycosylation motif, are naturally N-glycosylated in the mature viral glycoproteins, bind to major histocompatibility complex H-2D(b) molecules, and are immunogenic.