20 research outputs found
Biotin starvation causes mitochondrial protein hyperacetylation and partial rescue by the SIRT3-like deacetylase Hst4p
The essential vitamin biotin is a covalent and tenaciously attached prosthetic group in several carboxylases that play important roles in the regulation of energy metabolism. Here we describe increased acetyl-CoA levels and mitochondrial hyperacetylation as downstream metabolic effects of biotin deficiency. Upregulated mitochondrial acetylation sites correlate with the cellular deficiency of the Hst4p deacetylase, and a biotin-starvation-induced accumulation of Hst4p in mitochondria supports a role for Hst4p in lowering mitochondrial acetylation. We show that biotin starvation and knockout of Hst4p cause alterations in cellular respiration and an increase in reactive oxygen species (ROS). These results suggest that Hst4p plays a pivotal role in biotin metabolism and cellular energy homeostasis, and supports that Hst4p is a functional yeast homologue of the sirtuin deacetylase SIRT3. With biotin deficiency being involved in various metabolic disorders, this study provides valuable insight into the metabolic effects biotin exerts on eukaryotic cells
Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours
The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named ‘Immunoscore’ has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune). © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland
Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study
Objective To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations
Influence of the carbon source on production of cellulases, hemicellulases and pectinases by Trichoderma reesei Rut C-30
Recycling of process streams in ethanol production from softwoods based on enzymatic hydrolysis
Production of prebiotic xylooligosaccharides from alkaline extracted wheat straw using the K80R-variant of a thermostable alkali-tolerant xylanase
Dietary intake of different types and characteristics of processed meat which might be associated with cancer risk - results from the 24-hour diet recalls in the European Prospective Investigation into Cancer and Nutrition (EPIC)
Objective: There is increasing evidence for a significant effect of
processed meat (PM) intake on cancer risk. However, refined knowledge on
how components of this heterogeneous food group are associated with
cancer risk is still missing. Here, actual data on the intake of PM
subcategories is given; within a food-based approach we considered
preservation methods, cooking methods and nutrient content for
stratification, in order to address most of the aetiologically relevant
hypotheses.
Design and setting: Standardised computerised 24-hour diet recall
interviews were collected within the framework of the European
Prospective Investigation into Cancer and Nutrition (EPIC), a
prospective cohort study in 27 centres across 10 European countries.
Subjects: Subjects were 22 924 women and 13 031 men aged 35 - 74 years.
Results: Except for the so-called ‘health-conscious’ cohort in the UK,
energy-adjusted total PM intake ranged between 11.1 and 47.9 g day(-1)
in women and 18.8 and 88.5 g day(-1) in men. Ham, salami-type sausages
and heated sausages contributed most to the overall PM intake. The
intake of cured (addition of nitrate/nitrite) PM was highest in the
German, Dutch and northern European EPIC centres, with up to 68.8 g
day(-1) in men. The same was true for smoked PM (up to 51.8 g day(-1)).
However, due to the different manufacturing practice, the highest
average intake of NaNO2 through PM consumption was found for the Spanish
centres (5.4 mg day(-1) in men) as compared with German and British
centres. Spanish centres also showed the highest intake of NaCl-rich
types of PM; most cholesterol- and iron-rich PM was consumed in central
and northern European centres. Possibly hazardous cooking methods were
more often used for PM preparation in central and northern European
centres.
Conclusions: We applied a food-based categorisation of PM that addresses
aetiologically relevant mechanisms for cancer development and found
distinct differences in dietary intake of these categories of PM across
European cohorts. This predisposes EPIC to further investigate the role
of PM in cancer aetiology
Increased Risk for Substance Use-Related Problems in Autism Spectrum Disorders: A Population-Based Cohort Study
Dietary Fibre Intake and Risks of Cancers of the Colon and Rectum in the European Prospective Investigation into Cancer and Nutrition (EPIC)
Background: Earlier analyses within the EPIC study showed that dietary
fibre intake was inversely associated with colorectal cancer risk, but
results from some large cohort studies do not support this finding. We
explored whether the association remained after longer follow-up with a
near threefold increase in colorectal cancer cases, and if the
association varied by gender and tumour location.
Methodology/Principal Findings: After a mean follow-up of 11.0 years,
4,517 incident cases of colorectal cancer were documented. Total,
cereal, fruit, and vegetable fibre intakes were estimated from dietary
questionnaires at baseline. Hazard ratios (HRs) and 95% confidence
intervals (CIs) were estimated using Cox proportional hazards models
stratified by age, sex, and centre, and adjusted for total energy
intake, body mass index, physical activity, smoking, education,
menopausal status, hormone replacement therapy, oral contraceptive use,
and intakes of alcohol, folate, red and processed meats, and calcium.
After multivariable adjustments, total dietary fibre was inversely
associated with colorectal cancer (HR per 10 g/day increase in fibre
0.87, 95% CI: 0.79-0.96). Similar linear associations were observed for
colon and rectal cancers. The association between total dietary fibre
and risk of colorectal cancer risk did not differ by age, sex, or
anthropometric, lifestyle, and dietary variables. Fibre from cereals and
fibre from fruit and vegetables were similarly associated with colon
cancer; but for rectal cancer, the inverse association was only evident
for fibre from cereals.
Conclusions/Significance: Our results strengthen the evidence for the
role of high dietary fibre intake in colorectal cancer prevention