Mensch-Maschine-Systeme : Wissenschaftliches Kolloquium 5. März 2009, Fraunhofer IITB

Das informationstechnische Kolloquium Mensch-Maschine-Systeme des Fraunhofer IITB gibt anlässlich des 80sten Geburtstags seines ehemaligen Leiters und Präsidenten der Fraunhofer-Gesellschaft, Prof. Dr. Max Syrbe, einen Überblick über Geschichte, Stand und Trends der angewandten Forschung auf dem Gebiet der Mensch-Maschine-Systeme, welcher sich von der Ethik der Techniknutzung über die Automatisierungssysteme bis zu dem Maschinensehen für die Mensch-Maschine-Interaktion erstreckt

Mensch-Maschine-Systeme : Wissenschaftliches Kolloquium 5. März 2009, Fraunhofer IITB

Das informationstechnische Kolloquium Mensch-Maschine-Systeme des Fraunhofer IITB gibt anlässlich des 80sten Geburtstags seines ehemaligen Leiters und Präsidenten der Fraunhofer-Gesellschaft, Prof. Dr. Max Syrbe, einen Überblick über Geschichte, Stand und Trends der angewandten Forschung auf dem Gebiet der Mensch-Maschine-Systeme, welcher sich von der Ethik der Techniknutzung über die Automatisierungssysteme bis zu dem Maschinensehen für die Mensch-Maschine-Interaktion erstreckt

Modeling of mouse experiments suggests that optimal anti-hormonal treatment for breast cancer is diet-dependent

Estrogen receptor positive breast cancer is frequently treated with anti-hormonal treatment such as aromatase inhibitors (AI). Interestingly, a high body mass index has been shown to have a negative impact on AI efficacy, most likely due to disturbances in steroid metabolism and adipokine production. Here, we propose a mathematical model based on a system of ordinary differential equations to investigate the effect of high-fat diet on tumor growth. We inform the model with data from mouse experiments, where the animals are fed with high-fat or control (normal) diet. By incorporating AI treatment with drug resistance into the model and by solving optimal control problems we found differential responses for control and high-fat diet. To the best of our knowledge, this is the first attempt to model optimal anti-hormonal treatment for breast cancer in the presence of drug resistance. Our results underline the importance of considering high-fat diet and obesity as factors influencing clinical outcomes during anti-hormonal therapies in breast cancer patients.Comment: 44 pages, 21 figure

The Establishment of the Nordic Cardio-Oncology Society

Non peer reviewe

Treatment with aromatase inhibitors stimulates the expression of Epidermal growth factor receptor-1 and neuregulin 1 in ER positive \ HER-2neu non-amplified primary breast cancers

This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.jsbmb.2016.06.011While estrogens have been shown to modulate EGFR/HER-1 and HER-2/neu expression in experimental systems, the effects of estrogen deprivation on expression levels of the HER-receptors and the neuregulin (NRG)1 ligand in breast cancers remain unknown. Here, we measured EGFR/HER-1-4 and NRG1 mRNA in ER positive tumors from 85 postmenopausal breast cancer patients before and after two weeks (n = 64) and three months (n = 85) of primary treatment with an aromatase inhibitor (AI). In tumors lacking HER-2/neu amplification, quantitative real-time PCR analyses revealed EGFR/HER-1 and NRG1 to vary significantly between the three time points (before therapy, after 2 weeks and after 3 months on treatment; P ≤ 0.001 for both). Pair-wise comparison revealed a significant increase in EGFR/HER-1 already during the first two weeks of treatment (P = 0.049) with a further increase for both EGFR/HER-1 and NRG1 after 3 months on treatment (P ≤ 0.001 and P = 0.001 for both comparing values at 3 months to values at baseline and 2 weeks respectively). No difference between tumors responding versus non-responders was recorded. Further, no significant change in any parameter was observed among HER-2/neu amplified tumors. Analyzing components of the HER-2/neu PI3K/Akt downstream pathway, the PIK3CA H1047R mutation was associated with treatment response (P = 0.035); however no association between either AKT phosphorylation status or PIK3CA gene mutations and EGFR/HER-1 or NRG1 expression levels were observed. Our results indicate primary AI treatment to modulate expression of HER-family members and the growth factor NRG1 in HER-2/neu non-amplified breast cancers in vivo. Potential implications to long term sensitivity warrants further investigations.The study was supported by the Norwegian Cancer Society (https://kreftforeningen.no), The Western Norway Regional Health Authority (http://www.helse-bergen.no/forskning/samarbeidsorganet), Odd Fellow Medisinsk Vitenskapelig Forskningsfond (oddfellow.no) and Martin Flatners legat

Simultaneous Quantification of Aromatase Inhibitors and Estrogens in Postmenopausal Breast Cancer Patients

Context Currently there are no assays that can simultaneously quantify serum levels of the third-generation aromatase inhibitors (AIs): letrozole, anastrozole, and exemestane, and the ultra-low levels of estrogens in postmenopausal breast cancer patients on AI treatment. Such measurements may be pivotal for the determination of optimal and individualized treatment regimens. We aimed at developing a liquid chromatography–tandem mass spectrometry (MS/MS) method for simultaneous assessment of letrozole, anastrozole, exemestane, and 17-hydroxyexemestane as well as subpicomolar levels of estradiol and estrone. Methods Internal standards, calibrators, serum samples, and quality controls were in fully automated steps transferred to a deep-well plate for a 2-step liquid-liquid extraction. The extracts were reconstituted and analytes were separated chromatographically using 2 serially coupled columns, then subject to MS/MS in electrospray ionization mode. The method was thoroughly validated and is traceable to 2 accredited estrogen methods. Results The measurement range for estrone and estradiol was 0.2 to 12 000 pmol/L and 0.8 to 13 000 pmol/L, and covered the expected therapeutic range for the AIs. All analytes had a precision of less than or equal to 13%, and accuracies within 100 ± 8%. As proof of concept, AI and estrogen levels were determined in serum samples from postmenopausal breast cancer patients under treatment. Conclusion We present here an assay suitable for the simultaneous measurement of serum levels of all third-generation AIs and ultra-low levels of estrogens, providing a powerful new tool to study drug efficacy and compliance. The method is highly valuable for postmenopausal patients whose pretreatment estradiol levels are below the threshold of detection for most routine assays, but still require suppression.publishedVersio

Calculation of temperature distribution and effective temperature in high burnup fuel of WWER-1000

The problem of finding an effective temperature is highly important. This characteristic provides calculation of the power effect reactivity (PER), which defines safe and stable operation of nuclear reactor. The numerical experiment, which is considered on average and maximum heat load conditions, is put to find out changing of the effective temperature in the high burnup fuel of WWER-1000. In the course of the experiment mathematical statement of the problem is made, numerical solution of which is found with using the finite differences approximation of both control equations and border conditions. Also, the method of simple iteration is used for calculating temperature distributions, according to determination of the effective temperature. The linear approximation was obtained basing on effective and maximum temperatures depending on the burnup

The NAME trial:a direct comparison of classical oral Navelbine versus metronomic Navelbine in metastatic breast cancer

Chemotherapy for metastatic breast cancer (MBC) is in general given in cycles of maximum tolerated doses to potentially maximize the therapeutic outcome. However, when compared with targeted therapies for MBC, conventional and dose intensified chemotherapy has caused only modest survival benefits during the recent decades, often compromising the quality of life considerably. Navelbine is an antineoplastic agent that has shown efficacy in the treatment of a variety of cancer types, including breast cancer. Early clinical trials involving both breast cancer and lung cancer patients suggest that metronomic dosing of Navelbine might be at least as effective as classical administration (once weekly, etc.). The NAME trial compares these two strategies of Navelbine administration in MBC patients

MicroRNAs in the pathogenesis, diagnosis, prognosis and targeted treatment of cutaneous T-cell lymphomas

Cutaneous T-cell lymphoma (CTCL) represents a heterogeneous group of potentially devastating primary skin malignancies. Despite decades of intense research efforts, the pathogenesis is still not fully understood. In the early stages, both clinical and histopathological diagnosis is often difficult due to the ability of CTCL to masquerade as benign skin inflammatory dermatoses. Due to a lack of reliable biomarkers, it is also difficult to predict which patients will respond to therapy or progress towards severe recalcitrant disease. In this review, we discuss recent discoveries concerning dysregulated microRNA (miR) expression and putative pathological roles of oncogenic and tumor suppressive miRs in CTCL. We also focus on the interplay between miRs, histone deacetylase inhibitors, and oncogenic signaling pathways in malignant T cells as well as the impact of miRs in shaping the inflammatory tumor microenvironment. We highlight the potential use of miRs as diagnostic and prognostic markers, as well as their potential as therapeutic targets. Finally, we propose that the combined use of miR-modulating compounds with epigenetic drugs may provide a novel avenue for boosting the clinical efficacy of existing anti-cancer therapies in CTCL

<i>Staphylococcus aureus</i> enterotoxins induce FOXP3 in neoplastic T cells in Sézary syndrome

Sezary syndrome (SS) is a heterogeneous leukemic subtype of cutaneous T-cell lymphoma (CTCL) with generalized erythroderma, lymphadenopathy, and a poor prognosis. Advanced disease is invariably associated with severe immune dysregulation and the majority of patients die from infectious complications caused by microorganisms such as, Staphylococcus aureus, rather than from the lymphoma per se. Here, we examined if staphylococcal enterotoxins (SE) may shape the phenotype of malignant SS cells, including expression of the regulatory T-cell-associated marker FOXP3. Our studies with primary and cultured malignant cells show that SE induce expression of FOXP3 in malignant cells when exposed to nonmalignant cells. Mutations in the MHC class II binding domain of SE-A (SEA) largely block the effect indicating that the response relies at least in part on the MHC class II-mediated antigen presentation. Transwell experiments show that the effect is induced by soluble factors, partly blocked by anti-IL-2 antibody, and depends on STAT5 activation in malignant cells. Collectively, these findings show that SE stimulate nonmalignant cells to induce FOXP3 expression in malignant cells. Thus, differences in exposure to environmental factors, such as bacterial toxins may explain the heterogeneous FOXP3 expression in malignant cells in SS.Dermatology-oncolog