7 research outputs found
Exploration of associations between the FTO rs9939609 genotype, fasting and postprandial appetite-related hormones and perceived appetite in healthy men and women
Background:
The fat mass and obesity-associated gene (FTO) rs9939609 A-allele has been associated with obesity risk. Although the exact mechanisms involved remain unknown, the FTO rs9939609 A-allele has been associated with an impaired postprandial suppression of appetite.
Objectives:
To explore the influence of FTO rs9939609 genotype on fasting and postprandial appetite-related hormones and perceived appetite in a heterogeneous sample of men and women.
Design:
112 healthy men and women aged 18-50-years-old completed three laboratory visits for the assessment of FTO rs9939609 genotype, body composition, aerobic fitness, resting metabolic rate, visceral adipose tissue, liver fat, fasting leptin, and fasting and postprandial acylated ghrelin, total PYY, insulin, glucose and perceived appetite. Participants wore accelerometers for seven consecutive days for the assessment of physical activity and sedentary behaviour. Multivariable general linear models quantified differences between FTO rs9939609 groups for fasting and postprandial appetite outcomes, with and without the addition of a priori selected physiological and behavioural covariates. Sex-specific univariable Pearson's correlation coefficients were quantified between the appetite-related outcomes and individual characteristics.
Results:
95% confidence intervals for mean differences between FTO rs9939609 groups overlapped zero in unadjusted and adjusted general linear models for all fasting (PâŻâ„âŻ0.28) and postprandial (PâŻâ„âŻ0.19) appetite-related outcomes. Eta2 values for explained variance attributable to FTO rs9939609 were <5% for all outcomes. An exploratory correlation matrix indicated that associations between fasting and postprandial acylated ghrelin, total PYY and general or abdominal adiposity were also small (râŻ=âŻâ0.23 to 0.15, PâŻâ„âŻ0.09). Fasting leptin, glucose and insulin and postprandial insulin concentrations were associated with adiposity outcomes (râŻ=âŻ0.29 to 0.81, PâŻâ€âŻ0.033).
Conclusions:
Associations between the FTO rs9939609 genotype and fasting or postprandial appetite-related outcomes were weak in healthy men and women
Analysis of expression profiles of MAGE-A antigens in oral squamous cell carcinoma cell lines
<p>Abstract</p> <p>Background</p> <p>The immunological response to solid tumours is insufficient. Therefore, tumour specific antigens have been explored to facilitate the activation of the immune system. The cancer/testis antigen class of MAGE-A antigens is a possible target for vaccination. Their differential expression profiles also modulate the course of the cancer disease and its response to antineoplastic drugs.</p> <p>Methods</p> <p>The expression profiles of MAGE-A2, -A3, -A4, -A6 and -A10 in five own oral squamous cell carcinoma cell lines were characterised by rt-PCR, qrt-PCR and immunocytochemistry with a global MAGE-A antibody (57B) and compared with those of an adult keratinocyte cell line (NHEK).</p> <p>Results</p> <p>All tumour cell lines expressed MAGE-A antigens. The antigens were expressed in groups with different preferences. The predominant antigens expressed were MAGE-A2, -A3 and -A6. MAGE-A10 was not expressed in the cell lines tested. The MAGE-A gene products detected in the adult keratinocyte cell line NHEK were used as a reference.</p> <p>Conclusion</p> <p>MAGE-A antigens are expressed in oral squamous cell carcinomas. The expression profiles measured facilitate distinct examinations in forthcoming studies on responses to antineoplastic drugs or radiation therapy. MAGE-A antigens are still an interesting aim for immunotherapy.</p
True interindividual variability exists in postprandial appetite responses in healthy men but is not moderated by the FTO genotype
Background: After meal ingestion, a series of coordinated hormone responses occur
concomitantly with changes in perceived appetite. It is not known whether interindividual
variability in appetite exists in response to a meal. Objectives: This study aimed to 1) assess
the reproducibility of appetite responses to a meal; 2) quantify individual differences in
responses; and 3) explore any moderating influence of the fat mass and obesity associated
(FTO) gene. Methods: Using a replicated crossover design, 18 healthy men (mean ± SD 28.5
± 9.8 years, 27.0 ± 5.0 kg·m-2
) recruited according to FTO genotype (9 AA, 9 TT) completed
two identical control and two identical standardized meal conditions (5025 kJ) in randomized
sequences. Perceived appetite and plasma acylated ghrelin, total peptide YY (PYY), insulin
and glucose concentrations were measured before and after interventions as primary
outcomes. Interindividual differences were explored using Pearsonâs product-moment
correlations between the first and second replicate of the control-adjusted meal response.
Within-participant covariate-adjusted linear mixed models were used to quantify participant by-condition and genotype-by-condition interactions. Results: The meal suppressed acylated
ghrelin and appetite perceptions (standardized effect sizes (ES): 0.18-4.26) and elevated total
PYY, insulin and glucose (ES: 1.96-21.60). For all variables, SD of change scores was
greater in the meal versus control conditions. Moderate-to-large positive correlations were
observed between the two replicates of control-adjusted meal responses for all variables
(r=0.44-0.86, Pâ€0.070). Participant-by-condition interactions were present for all variables
(Pâ€0.056). FTO genotype-by-condition interactions were not significant (Pâ„0.19) and
treatment effect differences between genotype groups were small (ESâ€0.27) for all appetite
parameters. Conclusions: Reproducibility of postprandial appetite responses is generally
good. True interindividual variability is present beyond any random within-subject variation
in healthy men but is not moderated by the FTO genotype. These findings highlight the
3
importance of exploring individual differences in appetite for the prevention and/or treatment
of obesity. Clinical trial registry number: NCT03771690 (ClinicalTrials.gov)
Integrative analyses of gene expression and DNA methylation profiles in breast cancer cell line models of tamoxifen-resistance indicate a potential role of cells with stem-like properties
The Human Homolog of Drosophila Headcase Acts as a Tumor Suppressor through Its Blocking Effect on the Cell Cycle in Hepatocellular Carcinoma
Slit-2 facilitates interaction of P-cadherin with Robo-3 and inhibits cell migration in an oral squamous cell carcinoma cell line
Slits are a group of secreted glycoproteins that act as molecular guidance cues in cellular migration. Recently, several studies demonstrated that Slit-2 can operate as candidate tumour suppressor protein in various tissues. In this study, we show Slit-2 expression in basal cell layers of normal oral mucosa colocalized with P-cadherin expression. In contrast, there is a loss of Slit-2 and P-cadherin expression in mucosa of oral squamous cell carcinoma (OSCC). Our in vitro investigations reveal a correlation of P-cadherin and Slit-2 expression: OSCC cells with induced P-cadherin expression (PCI52_PC) display an increased Slit-2 expression. However, abrogating P-cadherin function with a function-blocking antibody decreases Slit-2 secretion confirming a direct link between P-cadherin and Slit-2. Moreover, experiments with OSCC cells show that Slit-2 interferes with a Wnt related signalling pathway, which in turn affects Slit-2 expression in a feedback loop. Functionally, transwell migration assays demonstrate a Slit-2 dose-dependent decrease of PCI52_PC cell migration. However, there is no influence on migration in mock control cells. Responsible for this migration block might be an interaction of P-cadherin with Roundabout (Robo)-3, a high affinity receptor of Slit-2. Indeed, proximity ligation assays exhibit P-cadherin/Robo-3 interactions on PCI52_PC cells. Additionally, we detect a modulation of this interaction by addition of recombinant Slit-2. Down-regulation of Robo-3 expression via small interfering RNA neutralizes Slit-2 induced migration block in PCI52_PC cells. In summary, our experiments show antitumorigenic effects of Slit-2 on P-cadherin expressing OSCC cells supposedly via modulation of Robo-3 interaction