28 research outputs found
Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance.
BACKGROUND: Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC.
METHODS: Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months.
RESULTS: TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38 mm (median tumour size; P=0.006, Mann-Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019).
CONCLUSIONS: We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies
BST2/Tetherin Enhances Entry of Human Cytomegalovirus
Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV) from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV
On the Origin of S0 Galaxies
I will review the basic properties of S0 galaxies in the local Universe in
relation to both elliptical and spiral galaxies, their neighbours on the Hubble
sequence, and also in relation to dwarf spheroidal (dSph) galaxies. This will
include colours, luminosities, spectral features, information about the age and
metallicity composition of their stellar populations and globular clusters,
about their ISM content, as well as kinematic signatures and their implications
for central black hole masses and past interaction events, and the number
ratios of S0s to other galaxy types in relation to environmental galaxy
density. I will point out some caveats as to their morphological discrimination
against other classes of galaxies, discuss the role of dust and the wavelength
dependence of bulge/disk light ratios. These effects are of importance for
investigations into the redshift evolution of S0 galaxies -- both as individual
objects and as a population. The various formation and transformation scenarios
for S0 and dSph galaxies will be presented and confronted with the available
observations.Comment: Invited Review, 18 pages, ``BARS 2004'' Conference, South Africa,
June 2004, eds.: K. C. Freeman, D. L. Block, I. Puerari, R. Groess, Kluwer,
in pres