TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophages (TAM) on histological grade of differentiation in colon carcinoma. Disruption of transforming growth factor beta (TGF-beta) signalling in tumour cells is related to more aggressive clinical behaviour. Expression data of components of this pathway in tumour-associated stroma is limited.</p> <p>Methods</p> <p>Tissue micro arrays of 310 colon carcinomas from curatively resected patients in UICC stage II and III were established. In a first step we quantified amount of CD68 positive TAMs and expression of components of TGF-beta signalling (TGF-beta1, TGF-beta receptors type 1 and 2, Smad 3 and 4) in tumour and associated stroma. Further we analyzed correlation to histological and clinical parameters (histological grade of differentiation (low-grade (i.e. grade 1 and 2) vs. high-grade (i.e. grade 3 and 4)), lymph node metastasis, distant metastasis, 5 year cancer related survival) using Chi-square or Fisher's exact test, when appropriate, to compare frequencies, Kaplan-Meier method to calculate 5-year rates of distant metastases and cancer-related survival and log rank test to compare the rates of distant metastases and survival. To identify independent prognostic factors Cox regression analysis including lymph node status and grading was performed.</p> <p>Results</p> <p>High-grade tumours and those with lymph node metastases showed higher rates of TAMs and lower expression of TGF-beta1. Loss of nuclear Smad4 expression in tumor was associated with presence of lymph node metastasis, but no influence on prognosis could be demonstrated. Decrease of both TGF-beta receptors in tumour-associated stroma was associated with increased lymph node metastasis and shorter survival. Stromal TGF-beta receptor 2 expression was an independent prognostic factor for cancer related survival.</p> <p>Conclusion</p> <p>Histological phenotype and clinical behaviour of colon cancer is not only influenced by mutational incidents in tumour cells but also affected by interaction of tumour tissue with inflammatory cells like macrophages and associated stroma and TGF-beta signalling is one important part of this crosstalk. Further studies are needed to elucidate the exact mechanisms.</p

Diet quality and colorectal tumor risk in persons with Lynch syndrome

Contains fulltext : 229397.pdf (Publisher’s version ) (Open Access)BACKGROUND: Persons with Lynch syndrome (LS) have an increased risk of developing colorectal tumors (CRTs). Adherence to diet quality indices associated with colorectal cancer (CRC) risk in the general population has not been studied before in LS. METHODS: Dietary habits of 490 participants with LS from a prospective cohort study was collected using a food frequency questionnaire. The Dutch Healthy Diet index 2015 (DHD15-index) and Dietary Approaches to Stop Hypertension (DASH) were used to score food-based diet quality. Diet quality scores were divided into tertiles where a higher tertile reflects a higher diet quality. Multivariable Cox proportional hazard regression models were used to estimate the association between the DHD15-index, DASH score and CRT risk. RESULTS: During a median follow-up time of 53.4 months, 210 participants (42.9%) developed CRTs. The DHD-index and DASH score were not associated with CRT risk; hazard ratios for highest vs. lowest tertile were 1.00 (95% Confidence Interval (CI): 0.67-1.48) and 1.11 (95% CI: 0.74-1.69), respectively. No linear trends across the DHD-index and DASH score tertiles were observed (P-trend = 0.97 and 0.83 respectively). CONCLUSION: In contrast to observations in the general population, no evidence for an association between the food-based DHD15-index or DASH score and CRT risk was observed in persons with LS. Further studies are needed investigating the association between diet quality and mechanisms leading to the development of LS-associated tumors

A common biological basis of obesity and nicotine addiction

J. Kaprio ja J. Tuomilehto työryhmien jäseniä (yht. 281).Peer reviewe

Enhanced wavelength-selective absorber for thermal detectors based on metamaterials

The dissipative electromagnetic energy absorption of tailored metamaterials can be exploited to improve the spectral sensitivity and selectivity of thermal detectors. The desired detector characteristics are engineered by tuning the single- or multiband absorption by resonance frequency, magnitude, and spectral bandwidth, strongly depending on the geometrical design of metamaterials. Here, the optical absorption properties of trilayer and multilayer resonant structures are investigated by numerical simulations. We consider isotropic, i.e., polarization-independent, disk-shaped absorber elements consisting of alternating aluminium and aluminium nitride layers of nanometer thicknesses, thus representing low-mass absorbers. Trilayer absorbers show spectral resonances at wavelengths between 2 and 6 µm, reaching near-unity absorption with peak bandwidths ranging from 0.45 to 1.05 µm. The absorption characteristics remain almost unchanged for radiation with an oblique incidence angle up to 40°. Resonant structures of multilayer absorber elements show besides spectral broadening a dual-band perfect absorption, which are suitable for simultaneous multispectral infrared imaging

Shape dependence of the magnetization reversal in sub-mu m magnetic tunnel junctions

Koop H, Brueckl H, Meyners D, Reiss G. Shape dependence of the magnetization reversal in sub-mu m magnetic tunnel junctions. JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS. 2004;272-276:E1475-E1476.In order to get access to resistance of very small junctions with lateral sizes down to 100 nm and below, we have set up a home-built conducting atomic force microscope which is able to contact the individual junctions with the tip and measure the tunnel magnetoresistance (TMR). The junctions are patterned by standard electron beam lithography. The influence of the element shape is investigated by analysing their switching behaviour in TMR minor loops and asteroids. In addition, numerical simulations of the magnetization reversal are carried out and compared to the experiment. (C) 2003 Elsevier B. V. All rights reserved

Single molecule detection with magnetic beads - computer simulation

Schepper W, Schotter J, Brueckl H, Reiss G. Single molecule detection with magnetic beads - computer simulation. JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS. 2004;272-276:E1695-E1696.The detection of single molecules, e. g. in biology is possible by marking the interesting molecules with magnetic beads and detect the influence of the beads on a GMR/TMR/SV multilayer. The development of suitable sensors has been studied experimentally as well as theoretically in order to optimize the sensor parameters. A FD method including the usually used contributions to the total energy ( exchange, af coupling, anisotropy and magnetostatic) is used for the simulation with additional contributions to the local field according to the stray fields of the beads. In this work, we present the results of micromagnetic calculations of the magnetization behavior of GMR/TMR sensors considering also the dipole fields of the beads as additional contributions to the local field. (C) 2003 Elsevier B. V. All rights reserved

Erlotinib treatment after platinum-based therapy in elderly patients with non-small-cell lung cancer in routine clinical practice – results from the ElderTac study

Abstract Background In this prospective non-interventional study, the effectiveness and tolerability of erlotinib in elderly patients with non-small-cell lung cancer (NSCLC) after ≥1 platinum-based chemotherapy were assessed. Methods A total of 385 patients ≥65 years of age with advanced NSCLC receiving erlotinib were observed over 12 months. The primary endpoint was the 1-year overall survival (OS) rate. Results Patients were predominantly Caucasian (99.2%), a mean of 73 years old; 24.7% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. Most common tumor histologies were adenocarcinoma (64.9%) and squamous cell carcinoma (22.3%). Of 119 patients tested, 15.1% had an activating epidermal growth factor receptor gene (EGFR) mutation. The 1-year OS rate was 31% (95% CI 25–36) with a median OS of 7.1 months (95% CI 6.0–7.9). OS was significantly better in females than males (p = 0.0258) and in patients with an EGFR mutation compared to EGFR wild-type patients (p = 0.0004). OS was not affected by age (p = 0.3436) and ECOG PS (p = 0.5364). Patients with squamous NSCLC tended to live longer than patients with non-squamous EGFR wild-type tumors (median OS: 8.6 vs 5.5 months). Cough and dyspnea improved during the observation period. The erlotinib safety profile was comparable to that in previous studies with rash (45.2%) and diarrhea (22.6%) being the most frequently reported adverse events. Conclusions Erlotinib represents a suitable palliative treatment option in further therapy lines for elderly patients with advanced NSCLC. The results obtained under real-life conditions add to our understanding of the benefits and risks of erlotinib in routine clinical practice. Trial registration BfArM (https://www.bfarm.de; ML23023); ClinicalTrials.gov (NCT01535729; 20 Feb 2012)