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1.
Leukemia ; 31(7): 1603-1610, 2017 07.
Article in English | MEDLINE | ID: mdl-27899804

ABSTRACT

The thymus is the major site for normal and leukemic T-cell development. The dissection of the molecular determinants of T-cell survival and differentiation is paramount for the manipulation of healthy or transformed T cells in cancer (immuno)therapy. Casein kinase 2 (CK2) is a serine/threonine protein kinase whose anti-apoptotic functions have been described in various hematological and solid tumors. Here we disclose an unanticipated role of CK2 in healthy human thymocytes that is selective to the γδ T-cell lineage. γδ thymocytes display higher (and T-cell receptor inducible) CK2 activity than their αß counterparts, and are strikingly sensitive to death upon CK2 inhibition. Mechanistically, we show that CK2 regulates the pro-survival AKT signaling pathway in γδ thymocytes and, importantly, also in γδ T-cell acute lymphoblastic leukemia (T-ALL) cells. When compared with healthy thymocytes or leukemic αß T cells, γδ T-ALL cells show upregulated CK2 activity, potentiated by CD27 costimulation, and enhanced apoptosis upon CK2 blockade using the chemical inhibitor CX-4945. Critically, this results in inhibition of tumor growth in a xenograft model of human γδ T-ALL. These data identify CK2 as a novel survival determinant of both healthy and leukemic γδ T cells, and may thus greatly impact their therapeutic manipulation.


Subject(s)
Casein Kinase II/physiology , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/immunology , Proto-Oncogene Proteins c-akt/physiology , Receptors, Antigen, T-Cell, gamma-delta/analysis , Signal Transduction/physiology , T-Lymphocytes/physiology , Thymus Gland/immunology , Animals , Casein Kinase II/antagonists & inhibitors , Cell Survival , Humans , Mice , Tumor Necrosis Factor Receptor Superfamily, Member 7/physiology
2.
J Med Microbiol ; 42(1): 3-9, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7739021

ABSTRACT

The non-immunoglobulin component of human milk responsible for the inhibition of Escherichia coli cell adhesion (haemagglutination) mediated by colonisation factor antigen 1 (CFA1) was determined by chromatographic fractionation of human whey proteins with Sephadex G-200, DEAE cellulose and heparin-sepharose. Pure free secretory component (fSC) and pure lactoferrin (Lf) were isolated and both compounds inhibited the haemagglutination induced by E. coli CFA1+. The lowest concentrations of purified fSC and Lf able to inhibit the haemagglutination induced by E. coli strain TR50/3 CFA1+ were 0.06 mg/ml and 0.1 mg/ml respectively. Commercially available lactoferrin from human milk and transferrin from human serum, which has a great structural analogy to lactoferrin, also inhibited the haemagglutination. The lowest concentrations of the commercial lactoferrin and transferrin able to inhibit the haemagglutination induced by E. coli TR50/3 CFA1+ were 0.03 mg/ml and 0.4 mg/ml, respectively. These results indicate that fSC and Lf may be important non-specific defence factors against enterotoxigenic E. coli infections.


Subject(s)
Bacterial Adhesion/drug effects , Escherichia coli/pathogenicity , Lactoferrin/pharmacology , Milk, Human/chemistry , Secretory Component/pharmacology , Chromatography, DEAE-Cellulose , Chromatography, Gel , Electrophoresis, Gel, Two-Dimensional , Electrophoresis, Polyacrylamide Gel , Enterotoxins/biosynthesis , Escherichia coli/drug effects , Hemagglutination/drug effects , Humans , Lactoferrin/isolation & purification , Milk, Human/immunology , Secretory Component/isolation & purification , Silver Staining , Transferrin/pharmacology
3.
J Trop Pediatr ; 39(3): 183-7, 1993 06.
Article in English | MEDLINE | ID: mdl-8326540

ABSTRACT

Haemolysin production (Hly) and mannose-resistant haemagglutination induction (MRHA) of human (H), bovine (B), and both (HB) erythrocytes was investigated in strains of E. coli isolated from 142 cases of children with diarrhoea aged 0-36 months. Haemolysin production was more frequent in strains isolated from children under 1 year and this characteristic was strongly associated with HB+ haemagglutination (P < 0.005). Isolation frequency of MRHA strains was compared in 53 breastfed and 50 non-breastfed children under 1 year of age. HB+ strains were significantly more frequent in non-breastfed infants (P < 0.025). Severity of diarrhoea evaluated by the number of watery stools per day, was significantly reduced in the breastfed group (P < 0.05). The results suggests that breastfeeding may protect infants against the establishment of HB+ strains which might be acting either as a main pathogen or as an opportunistic strain.


Subject(s)
Breast Feeding , Diarrhea, Infantile/microbiology , Escherichia coli/isolation & purification , Fimbriae Proteins , Antigens, Bacterial/analysis , Bacterial Proteins/analysis , Child, Preschool , Escherichia coli/metabolism , Hemagglutination , Hemolysin Proteins/biosynthesis , Humans , Infant , Infant, Newborn , Mannose/pharmacology , Milk, Human/immunology
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