4 research outputs found
The Swiss Approach - feasibility of a national low-dose CT lung cancer screening program.
BACKGROUND
Lung cancer is the leading cause of cancer-related deaths in Switzerland. Despite this, there is no lung cancer screening program in the country. In the United States, low-dose computed tomography (LDCT) lung cancer screening is partially established and endorsed by guidelines. Moreover, evidence is growing that screening reduces lung cancer-related mortality and this was recently shown in a large European randomized controlled trial. Implementation of a lung cancer screening program, however, is challenging and depends on many country-specific factors. The goal of this article is to outline a potential Swiss lung cancer screening program.
FRAMEWORK
An exhaustive literature review on international screening models as well as interviews and site visits with international experts were initiated. Furthermore, workshops and interviews with national experts and stakeholders were conducted to share experiences and to establish the basis for a national Swiss lung cancer screening program.
SCREENING APPROACH
General practitioners, pulmonologists and the media should be part of the recruitment process. Decentralisation of the screening might lead to a higher adherence rate. To reduce stigmatisation, the screening should be integrated in a "lung health check". Standardisation and a common quality level are mandatory. The PLCOm2012 risk calculation model with a threshold of 1.5% risk for developing cancer in the next six years should be used in addition to established inclusion criteria. Biennial screening is preferred. LUNG RADS and NELSON+ are applied as classification models for lung nodules.
CONCLUSION
Based on data from recent studies, literature research, a health technology assessment, the information gained from this project and a pilot study the Swiss Interest Group for lung cancer screening (CH-LSIG) recommends the timely introduction of a systematic lung cancer screening program in Switzerland. The final decision is for the Swiss Cancer Screening Committee to make
The Swiss Approach - feasibility of a national low-dose CT lung cancer screening program
BACKGROUND
Lung cancer is the leading cause of cancer-related deaths in Switzerland. Despite this, there is no lung cancer screening program in the country. In the United States, low-dose computed tomography (LDCT) lung cancer screening is partially established and endorsed by guidelines. Moreover, evidence is growing that screening reduces lung cancer-related mortality and this was recently shown in a large European randomized controlled trial. Implementation of a lung cancer screening program, however, is challenging and depends on many country-specific factors. The goal of this article is to outline a potential Swiss lung cancer screening program.
FRAMEWORK
An exhaustive literature review on international screening models as well as interviews and site visits with international experts were initiated. Furthermore, workshops and interviews with national experts and stakeholders were conducted to share experiences and to establish the basis for a national Swiss lung cancer screening program.
SCREENING APPROACH
General practitioners, pulmonologists and the media should be part of the recruitment process. Decentralisation of the screening might lead to a higher adherence rate. To reduce stigmatisation, the screening should be integrated in a "lung health check". Standardisation and a common quality level are mandatory. The PLCOm2012 risk calculation model with a threshold of 1.5% risk for developing cancer in the next six years should be used in addition to established inclusion criteria. Biennial screening is preferred. LUNG RADS and NELSON+ are applied as classification models for lung nodules.
CONCLUSION
Based on data from recent studies, literature research, a health technology assessment, the information gained from this project and a pilot study the Swiss Interest Group for lung cancer screening (CH-LSIG) recommends the timely introduction of a systematic lung cancer screening program in Switzerland. The final decision is for the Swiss Cancer Screening Committee to make
Car-2-Car Communication Consortium - Manifesto
This document summarizes and describes the main building blocks of the Car2X Communication System as it is pursued by the Car2Car Communication Consortium (C2C-CC). âCar2Xâ means interactions among cars, between cars and infrastructures, and viceversa. It provides interested readers with an introduction to Car2X communications. It is intended to be a living document which will be complemented according to the progress of the work of the C2C-CC. One main objective of this document is to give insight into ongoing and upcoming activities, such as public funded projects which target to contribute to the C2C-CC specifications, an overview on ongoing work and results achieved so far. In addition, this document provides concepts and technologies that have been developed or identified by the C2C-CC and assessed as necessary building blocks to be proposed for a standard
Nicotinamide-N-methyltransferase is a promising metabolic drug target for primary and metastatic clear cell renal cell carcinoma
BACKGROUND: The metabolic enzyme nicotinamideâNâmethyltransferase (NNMT) is highly expressed in various cancer entities, suggesting tumourâpromoting functions. We systematically investigated NNMT expression and its metabolic interactions in clear cell renal cell carcinoma (ccRCC), a prominent RCC subtype with metabolic alterations, to elucidate its role as a drug target. METHODS: NNMT expression was assessed in primary ccRCC (n = 134), nonâtumour tissue and ccRCCâderived metastases (n = 145) by microarray analysis and/or immunohistochemistry. Findings were validated in The Cancer Genome Atlas (kidney renal clear cell carcinoma [KIRC], n = 452) and by singleâcell analysis. Expression was correlated with clinicopathological data and survival. Metabolic alterations in NNMTâdepleted cells were assessed by nontargeted/targeted metabolomics and extracellular flux analysis. The NNMT inhibitor (NNMTi) alone and in combination with the inhibitor 2âdeoxyâDâglucose for glycolysis and BPTES (bisâ2â(5âphenylacetamidoâ1,3,4âthiadiazolâ2âyl)ethylâsulfide) for glutamine metabolism was investigated in RCC cell lines (786âO, A498) and in two 2D ccRCCâderived primary cultures and three 3D ccRCC airâliquid interface models. RESULTS: NNMT protein was overexpressed in primary ccRCC (p = 1.32 Ă 10(â16)) and ccRCCâderived metastases (p = 3.92 Ă 10(â20)), irrespective of metastatic location, versus nonâtumour tissue. Singleâcell data showed predominant NNMT expression in ccRCC and not in the tumour microenvironment. High NNMT expression in primary ccRCC correlated with worse survival in independent cohorts (primary RCCâhazard ratio [HR] = 4.3, 95% confidence interval [CI]: 1.5â12.4; KIRCâHR = 3.3, 95% CI: 2.0â5.4). NNMT depletion leads to intracellular glutamine accumulation, with negative effects on mitochondrial function and cell survival, while not affecting glycolysis or glutathione metabolism. At the gene level, NNMTâdepleted cells upregulate glycolysis, oxidative phosphorylation and apoptosis pathways. NNMTi alone or in combination with 2âdeoxyâDâglucose and BPTES resulted in inhibition of cell viability in ccRCC cell lines and primary tumour and metastasisâderived models. In two out of three patientâderived ccRCC airâliquid interface models, NNMTi treatment induced cytotoxicity. CONCLUSIONS: Since efficient glutamine utilisation, which is essential for ccRCC tumours, depends on NNMT, smallâmolecule NNMT inhibitors provide a novel therapeutic strategy for ccRCC and act as sensitizers for combination therapies