Редокс-регуляция динамического характера фенотипа эндотелиоцитов кровеносных сосудов

ЭНДОТЕЛИАЛЬНЫЕ КЛЕТКИКЛЕТКИЭНДОТЕЛИЙКРОВЕНОСНЫЕ СОСУДЫФЕНОТИПГЕНЕТИЧЕСКИЕ ФЕНОМЕНЫОКИСЛИТЕЛЬНО-ВОССТАНОВИТЕЛЬНЫЕ РЕАКЦИИЭНЕРГЕТИЧЕСКИЙ ОБМЕНПЕРЕКИСНОЕ ОКИСЛЕНИЕ ЛИПИДО

High Tumour Cannabinoid CB1 Receptor Immunoreactivity Negatively Impacts Disease-Specific Survival in Stage II Microsatellite Stable Colorectal Cancer

BACKGROUND: There is good evidence in the literature that the cannabinoid system is disturbed in colorectal cancer. In the present study, we have investigated whether CB(1) receptor immunoreactive intensity (CB(1)IR intensity) is associated with disease severity and outcome. METHODOLOGY/PRINCIPAL FINDINGS: CB(1)IR was assessed in formalin-fixed, paraffin-embedded specimens collected with a consecutive intent during primary tumour surgical resection from a series of cases diagnosed with colorectal cancer. Tumour centre (n = 483) and invasive front (n = 486) CB(1)IR was scored from 0 (absent) to 3 (intense staining) and the data was analysed as a median split i.e. CB(1)IR <2 and ≥2. In microsatellite stable, but not microsatellite instable tumours (as adjudged on the basis of immunohistochemical determination of four mismatch repair proteins), there was a significant positive association of the tumour grade with the CB(1)IR intensity. The difference between the microsatellite stable and instable tumours for this association of CB(1)IR was related to the CpG island methylation status of the cases. Cox proportional hazards regression analyses indicated a significant contribution of CB(1)IR to disease-specific survival in the microsatellite stable tumours when adjusting for tumour stage. For the cases with stage II microsatellite stable tumours, there was a significant effect of both tumour centre and front CB(1)IR upon disease specific survival. The 5 year probabilities of event-free survival were: 85±5 and 66±8%; tumour interior, 86±4% and 63±8% for the CB(1)IR<2 and CB(1)IR≥2 groups, respectively. CONCLUSIONS/SIGNIFICANCE: The level of CB(1) receptor expression in colorectal cancer is associated with the tumour grade in a manner dependent upon the degree of CpG hypermethylation. A high CB(1)IR is indicative of a poorer prognosis in stage II microsatellite stable tumour patients

Statement on Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment

The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, “Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment” was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages: We are at a turning point: multiple exposures and their combined effects require better management to protect public health and the environment from hazardous chemical mixtures. Regulatory initiatives should be launched to investigate the opportunities for all relevant regulatory frameworks to include prospective mixture risk assessment and consider combined exposures to (real-life) chemical mixtures to humans and wildlife, across sectors. Precautionary approaches and intermediate measures (e.g. Mixture Assessment Factor) can already be applied, although, definitive mixture risk assessments cannot be routinely conducted due to significant knowledge and data gaps. A European strategy needs to be set, through stakeholder engagement, for the governance of combined exposure to multiple chemicals and mixtures. The strategy would include research aimed at scientific advancement in mechanistic understanding and modelling techniques, as well as research to address regulatory and policy needs. Without such a clear strategy, specific objectives and common priorities, research, and policies to address mixtures will likely remain scattered and insufficient

Prognostic factors in colorectal cancer : aspects of tumour dissemination

Diss. (sammanfattning) Umeå : Umeå universitet, 2002digitalisering@um

Behov av robusta verktyg för miljöbedömning inom byggsektorn - en projektsammanfattning

Cirka 40 procent av all resursanvändning i forma av material och energi sker i byggsektorn. I arbetet med att vrida hela samhället mot en totalt sett lägre miljöbelastning spelar byggsektorn därmed en viktig roll

Behov av robusta verktyg för miljöbedömning inom byggsektorn - en projektsammanfattning

Cirka 40 procent av all resursanvändning i forma av material och energi sker i byggsektorn. I arbetet med att vrida hela samhället mot en totalt sett lägre miljöbelastning spelar byggsektorn därmed en viktig roll