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Planegg, Germany

Eichner J.,University of Tubingen | Heubach Y.,Reutlingen University | Ruff M.,University of Tubingen | Kohlhof H.,4SC AG | And 5 more authors.
BioSystems | Year: 2014

Background and scope: Today, web-based data analysis pipelines exist for a wide variety of microarray platforms, such as ordinary gene-centered arrays, exon arrays and SNP arrays. However, most of the available software tools provide only limited support for reverse-phase protein arrays (RPPA), as relevant inherent properties of the corresponding datasets are not taken into account. Thus, we developed the web-based data analysis pipeline RPPApipe, which was specifically tailored to suit the characteristics of the RPPA platform and encompasses various tools for data preprocessing, statistical analysis, clustering and pathway analysis. Implementation and performance: All tools which are part of the RPPApipe software were implemented using R/Bioconductor. The software was embedded into our web-based ZBIT Bioinformatics Toolbox which is a customized instance of the Galaxy platform. Availability: RPPApipe is freely available under GNU Public License from http://webservices.cs.uni-tuebingen.de. A full documentation of the tool can be found on the corresponding website http://www.cogsys.cs.uni-tuebingen.de/software/RPPApipe. © 2014 Elsevier Ireland Ltd. Source


The invention relates to methods for testing the response of spheroids to exposure with therapeutics. Preferably the spheroids are derived from primary isolate biological tissue and/or cell-containing bodily fluid. Further embodiments relate to spheroid sections and arrays including kits suitable for carrying out the method according to the present invention.


Patent
SpheroTec GmbH | Date: 2015-09-07

The invention pertains to a process for the preparation of multicellular spheroids from a suspension of single cells, wherein the cells are directly derived from a biological tissue and/or from cell-containing bodily fluid. The invention is further directed to the multicellular spheroids obtained by the process according to the invention as well as to the use of the spheroids for diagnostic, screening and therapeutic purposes.


Patent
SpheroTec GmbH | Date: 2015-05-11

The invention relates to a process for generating fibroblasts, more particularly, to the culturing of fibroblasts in large numbers and of the heterogenic type. The invention is also directed to the use of fibroblasts in the preparation of heterotypic spheroids and a process for the preparation of such heterotypic spheroids.


Halfter K.,SpheroTec GmbH | Hoffmann O.,SpheroTec GmbH | Ditsch N.,Ludwig Maximilians University of Munich | Ahne M.,SpheroTec GmbH | And 5 more authors.
Journal of Translational Medicine | Year: 2016

Background: Targeted anti-HER2 therapy has greatly improved the prognosis for many breast cancer patients. However, treatment for HER2 negative disease is currently still selected from a multitude of untargeted chemotherapeutic treatment options. A predictive test was developed using patient-derived spheroids to identify the most effective therapy for patients with HER2 negative breast cancer of all stages, for clinically relevant subgroups, as well as individual patients. Methods: Tumor samples from 120 HER2 negative patients obtained through biopsy or surgical excision were tested in the breast cancer spheroid model using scaffold-free cell culture. Similarly, spheroids were also generated from established HER2 negative breast cancer cell lines T-47D, MCF7, HCC1143, and HCC1937 to compare treatment efficacy of heterogeneous cell populations from patient tumor tissue with homogeneous cell lines. Spheroids were treated in vitro with guideline-recommended compounds. Treatment mediated impact on cell survival was subsequently quantified using an ATP assay. Results: Differences were observed in the metabolic activity of the untreated spheroids, whereby cell lines consistently achieved higher values compared to tissue spheroids (p<0.001). A higher number of cells per spheroid correlated with a higher basal metabolic activity in tissue-derived spheroids (p<0.01), while the opposite was observed for cell line spheroids (p<0.01). Recurrent tumors showed a higher mean vitality (p<0.01) compared to primary tumors. Except for taxanes, treatment efficacy for most tested compounds differed significantly between breast cancer tissue spheroids and breast cancer cell lines. Overall a high variability in treatment response in vitro was seen in the tissue spheroids regardless of the tested substances. A greater response to anthracycline/docetaxel was observed for hormone receptor negative samples (p<0.01). A higher response to 5-FU (p<0.01) and anthracycline (p<0.05) was seen in high grade tumors. Smaller tumor size and negative lymph node status were both associated with a higher treatment efficacy to anthracycline treatment combined with 5-FU (cT1/2 vs cT3/4, p=0.035, cN+vs cN-, p<0.05). Conclusions: The tissue spheroid model reflects current guideline treatment recommendations for HER2 negative breast cancer, whereas tested cell lines did not. This model represents a unique diagnostic method to select the most effective therapy out of several equivalent treatment options. © 2016 Halfter et al. Source

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