University of Münster

About: University of Münster is a education organization based out in Münster, Germany. It is known for research contribution in the topics: Population & Catalysis. The organization has 35609 authors who have published 69059 publications receiving 2278534 citations. The organization is also known as: University of Munster & University of Muenster.

Re: Leptin—A Growth Factor in Normal and Malignant Breast Cells and for Normal Mammary Gland Development

Abstract: BACKGROUND Obesity is a risk factor for breast cancer in postmenopausal women. As body weight and fat mass increase, circulating leptin increases. Leptin is an adipocyte-derived cytokine that acts through the long form of its receptor, termed OB-Rb. To investigate whether leptin is associated with breast cancer, we determined the expression of OB-Rb in human breast epithelial HBL100 cells and human breast carcinoma-derived T-47D cells, determined whether leptin influenced the proliferation of these cells, and evaluated the structure of mammary tissue in genetically obese leptin-deficient Lep(ob)Lep(ob) and leptin receptor-deficient Lepr(db)Lepr(db) mice. METHODS Cell numbers and cell colony formation by HBL100 and T-47D cells were determined by anchorage-dependent and anchorage-independent growth assays. OB-Rb expression was examined by reverse transcription-polymerase chain reaction and immunoblot analyses. Expression of leptin signaling pathway components was evaluated with immunoblot and electrophoretic mobility shift assays. Mammary gland development in lean and obese mice was investigated in whole-mount studies. All statistical tests were two-sided. RESULTS Leptin enhanced anchorage-dependent proliferation by 138% (95% confidence interval [CI] = 108% to 169%) in T-47D cells and 50% (95% CI = 38% to 60%) in HBL100 cells. In both cell lines, OB-Rb was expressed, and leptin increased the expression of phosphorylated signal transducers and activators of transcription 3 (STAT3), phosphorylated extracellular signal-regulated kinase (ERK), and transcript activator protein 1 (AP-1). However, leptin increased anchorage-independent cell growth only in the breast cancer cell line (by 81% [95% CI = 62% to 101%] compared with untreated cells). Obese Lep(ob)Lep(ob) and Lepr(db)Lepr(db) mice had minimal epithelial development in the mature mammary gland compared with their lean counterparts. CONCLUSIONS Leptin appears to be able to control the proliferation of both normal and malignant breast epithelial cells. Consequently, the leptin pathway should be further studied as a target for interventions to treat or prevent breast cancer.

Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp.

Abstract: Cancer chemotherapy resistance (MDR) is the innate and/or acquired ability of cancer cells to evade the effects of chemotherapeutics and is one of the most pressing major dilemmas in cancer therapy. Chemotherapy resistance can arise due to several host or tumor-related factors. However, most current research is focused on tumor-specific factors and specifically genes that handle expression of pumps that efflux accumulated drugs inside malignantly transformed types of cells. In this work, we suggest a wider and alternative perspective that sets the stage for a future platform in modifying drug resistance with respect to the treatment of cancer.

Reduced basis method for finite volume approximations of parametrized linear evolution equations

Abstract: The model order reduction methodology of reduced basis (RB) techniques offers efficient treatment of parametrized partial differential equations (P2 DEs) by providing both approximate solution procedures and efficient error estimates. RB-methods have so far mainly been applied to finite element schemes for elliptic and parabolic problems. In the current study we extend the methodology to general linear evolution schemes such as finite volume schemes for parabolic and hyperbolic evolution equations. The new theoretic contributions are the formulation of a reduced basis approximation scheme for these general evolution problems and the derivation of rigorous a-posteriori error estimates in various norms. Algorithmically, an offline/online decomposition of the scheme and the error estimators is realized in case of affine parameter-dependence of the problem. This is the basis for a rapid online computation in case of multiple simulation requests. We introduce a new offline basis-generation algorithm based on our a-posteriori error estimator which combines ideas from existing approaches. Numerical experiments for an instationary convection-diffusion problem demonstrate the efficient applicability of the approach.

Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force

Abstract: Background Therapeutic targets have been defined for diseases like diabetes, hypertension or rheumatoid arthritis and adhering to them has improved outcomes. Such targets are just emerging for spondyloarthritis (SpA). Objective To define the treatment target for SpA including ankylosing spondylitis and psoriatic arthritis (PsA) and develop recommendations for achieving the target, including a treat-to-target management strategy. Methods Based on results of a systematic literature review and expert opinion, a task force of expert physicians and patients developed recommendations which were broadly discussed and voted upon in a Delphi-like process. Level of evidence, grade and strength of the recommendations were derived by respective means. The commonalities between axial SpA, peripheral SpA and PsA were discussed in detail. Results Although the literature review did not reveal trials comparing a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated the development of recommendations. The group agreed on 5 overarching principles and 11 recommendations; 9 of these recommendations related commonly to the whole spectrum of SpA and PsA, and only 2 were designed separately for axial SpA, peripheral SpA and PsA. The main treatment target, which should be based on a shared decision with the patient, was defined as remission, with the alternative target of low disease activity. Follow-up examinations at regular intervals that depend on the patient9s status should safeguard the evolution of disease activity towards the targeted goal. Additional recommendations relate to extra-articular and extramusculoskeletal aspects and other important factors, such as comorbidity. While the level of evidence was generally quite low, the mean strength of recommendation was 9–10 (10: maximum agreement) for all recommendations. A research agenda was formulated. Conclusions The task force defined the treatment target as remission or, alternatively, low disease activity, being aware that the evidence base is not strong and needs to be expanded by future research. These recommendations can inform the various stakeholders about expert opinion that aims for reaching optimal outcomes of SpA.