Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters










Database
Language
Publication year range
1.
Cancers (Basel) ; 15(20)2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37894361

ABSTRACT

BACKGROUND: Prostate cancer is the most commonly diagnosed malignancy and the sixth leading cause of cancer death in men worldwide. Chromosomal instability (CIN) and polyploid giant cancer cells (PGCCs) have been considered predominant hallmarks of cancer. Recent clinical studies have proven the association of CIN, aneuploidy, and PGCCs with poor prognosis of prostate cancer (PCa). Evidence of HCMV transforming potential might indicate that HCMV may be involved in PCa. METHODS: Herein, we underline the role of the high-risk HCMV-DB and -BL clinical strains in transforming prostate epithelial cells and assess the molecular and cellular oncogenic processes associated with PCa. RESULTS: Oncogenesis parallels a sustained growth of "CMV-Transformed Prostate epithelial cells" or CTP cells that highly express Myc and EZH2, forming soft agar colonies and displaying stemness as well as mesenchymal features, hence promoting EMT as well as PGCCs and a spheroid appearance. CONCLUSIONS: HCMV-induced Myc and EZH2 upregulation coupled with stemness and EMT traits in IE1-expressing CTP might highlight the potential role of HCMV in PCa development and encourage the use of anti-EZH2 and anti-HCMV in PCa treatment.

2.
Cancers (Basel) ; 13(7)2021 Mar 29.
Article in English | MEDLINE | ID: mdl-33805340

ABSTRACT

The tumor microenvironment plays a major role in tumor growth, invasion and resistance to chemotherapy, however understanding how all actors from microenvironment interact together remains a complex issue. The tumor microenvironment is classically represented as three closely connected components including the stromal cells such as immune cells, fibroblasts, adipocytes and endothelial cells, the extracellular matrix (ECM) and the cytokine/growth factors. Within this space, proteins of the adamalysin family (ADAM for a disintegrin and metalloproteinase; ADAMTS for ADAM with thrombospondin motifs; ADAMTSL for ADAMTS-like) play critical roles by modulating cell-cell and cell-ECM communication. During last decade, the implication of adamalysins in the development of hepatocellular carcinoma (HCC) has been supported by numerous studies however the functional characterization of most of them remain unsettled. In the present review we propose both an overview of the literature and a meta-analysis of adamalysins expression in HCC using data generated by The Cancer Genome Atlas (TCGA) Research Network.

3.
Virology ; 481: 34-42, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25765005

ABSTRACT

Hepatitis B virus (HBV) infection is a major public health problem. Recently, the human liver bile acid transporter Na(+)/taurocholate cotransporting polypeptide (NTCP) has been identified as an HBV specific receptor. NTCP expression is known to be strongly regulated by IL-6. This study was aimed at characterizing the effect of IL-6 on HBV entry. HBV entry was inhibited by up to 90% when cells were pretreated with IL-6 as shown by a strong inhibition of long term HBsAg secretion. This effect was confirmed by showing a severe reduction of intracellular HBV cccDNA. In parallel, we observed a 98% decrease in NTCP mRNA steady state level and an 80% reduction in NTCP-mediated taurocholate uptake. IL-6-mediated inhibition of NTCP-mediated taurocholate uptake and viral entry exhibited similar dose-dependence and kinetics while restoration of NTCP expression suppressed the inhibitory effect of IL-6. NTCP-mediated HBV entry is therefore markedly inhibited by IL-6.


Subject(s)
Down-Regulation , Hepatitis B virus/physiology , Hepatitis B/genetics , Interleukin-6/metabolism , Organic Anion Transporters, Sodium-Dependent/genetics , Symporters/genetics , Virus Internalization , Hep G2 Cells , Hepatitis B/metabolism , Hepatitis B/virology , Hepatitis B virus/genetics , Hepatocytes/metabolism , Hepatocytes/virology , Humans , Interleukin-6/genetics , Organic Anion Transporters, Sodium-Dependent/metabolism , Receptors, Virus/genetics , Receptors, Virus/metabolism , Symporters/metabolism
4.
FEBS Lett ; 589(2): 193-200, 2015 Jan 16.
Article in English | MEDLINE | ID: mdl-25481411

ABSTRACT

To improve a previously constructed broadly neutralizing hepatitis B virus (HBV)-specific preS1 humanized antibody (HzKR127), we further humanized it through specificity-determining residue (SDR) grafting. Moreover, we improved affinity by mutating two residues in heavy-chain complementarity-determining regions (CDR), on the basis of the crystal structure of the antigen-antibody complex. HzKR127-3.2 exhibited 2.5-fold higher affinity and enhanced virus-neutralizing activity compared to the original KR127 antibody and showed less immunogenic potential than HzKR127. Enhanced virus-neutralizing activity was achieved by the increased association rate, providing insights into engineering potent antibody therapeutics for HBV immunoprophylaxis. HzKR127-3.2 may be a good candidate for HBV immunoprophylaxis.


Subject(s)
Antigen-Antibody Complex , Hepatitis B Antibodies/chemistry , Hepatitis B Antibodies/immunology , Hepatitis B virus/immunology , Amino Acid Sequence , Animals , Cell Line , Epitopes, T-Lymphocyte/immunology , Hepatitis B Antibodies/pharmacology , Humans , Mice , Models, Molecular , Molecular Sequence Data , Protein Structure, Tertiary , Viral Proteins/chemistry , Viral Proteins/immunology
5.
Toxicology ; 300(1-2): 46-56, 2012 Oct 09.
Article in English | MEDLINE | ID: mdl-22683347

ABSTRACT

Inorganic arsenic is a toxic environmental contaminant to which humans are mainly exposed through drinking water. This metalloid impairs functions of several key immune cells. Particularly, it reduces IL-2 secretion and proliferation of blood peripheral mononuclear cells stimulated by lectins that, however, do not mimic physiological T cell activation. The present study used isolated human T cells activated, in a more physiological manner, through stimulation with CD3/CD28 antibodies, to carefully analyze the impact of arsenic on T cell proliferation and cytokine expression. We demonstrate that non cytotoxic concentrations of sodium arsenite (As(III), 0.25-2µM) significantly reduce T cell proliferation by increasing the percentage of non dividing cells blocked in G1 phase and by preventing cyclin D3 and CDC25A expression. They also markedly, although not totally, reduces IL-2 expression at both mRNA and protein levels; however, metalloid-dependent inhibition of T cells could not be reversed by addition of recombinant IL-2. In addition, As(III) markedly reduces secretion of interferon-γ without impairing that of IL-4 and IL-13; it also decreases interferon-γ mRNA levels but increases those of IL-13. Finally, simultaneously to its immune effects, As(III) rapidly and potently increases expression of the redox-sensitive genes HMOX1, NQO1 and GCLM in activated T cells without altering the levels of reactive oxygen species. In conclusion, our results demonstrate that As(III) inhibits T cell proliferation, independently of IL-2, and alters the Th balance of cytokines secreted by co-stimulated T cells which thus constitute direct targets of this major environmental contaminant.


Subject(s)
Arsenicals/adverse effects , Cell Proliferation/drug effects , Cytokines/biosynthesis , T-Lymphocytes/drug effects , Arsenites/adverse effects , Cyclin D3/analysis , Cyclin D3/biosynthesis , Cytokines/analysis , Flow Cytometry , G1 Phase/drug effects , Humans , Interferon-gamma/analysis , Interferon-gamma/biosynthesis , Interleukin-13/analysis , Interleukin-13/biosynthesis , Interleukin-2/analysis , Interleukin-2/biosynthesis , Interleukin-4/analysis , Interleukin-4/biosynthesis , Lymphocyte Activation/drug effects , Reactive Oxygen Species/analysis , Real-Time Polymerase Chain Reaction , Sodium Compounds/adverse effects , T-Lymphocytes/chemistry , T-Lymphocytes/metabolism , T-Lymphocytes/physiology
SELECTION OF CITATIONS
SEARCH DETAIL
...