Oncotest GmbH

Freiburg, Germany

Oncotest GmbH

Freiburg, Germany
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News Article | May 16, 2017
Site: www.businesswire.com

WILMINGTON, Mass.--(BUSINESS WIRE)--Charles River Laboratories International, Inc. (NYSE: CRL) recently announced updates to its expanding oncology discovery business, including significant additions to its online Tumor Model Compendium. The Compendium provides oncology researchers with a resource to identify and locate targeted, suitable patient-derived xenografts (PDXs) based on specific histology and molecular properties, and now includes additional molecular characteristics for syngeneic models. “The use of a human tumor graft in a humanized model represents the future of immuno-oncology research,” said Birgit Girshick, Corporate Senior Vice President, Global Discovery, at Charles River. “A model that more closely mirrors human immune systems allows researchers to conduct groundbreaking studies more efficiently and effectively, with the goal of developing more translational therapies. Utilizing the Tumor Model Compendium, oncology researchers can identify the exact tumor model and target for their research, getting them that much closer to that goal.” Charles River has more than 450 fully characterized proprietary PDXs in its portfolio, which represents all major tumor histotypes, and provides extensive background and characterization for oncology research. The most recent Compendium update expands the existing tumor model collection to include: Recognizing the importance of selecting the appropriate tumor model for in vivo and in vitro oncology, Charles River partnered with OcellO to further expand their capabilities with PDX models. Through their agreement, OcellO utilizes human tumor material from Charles River PDX models and applies it in their 3D cell culture drug screening platform. This high-throughput platform enables the growth of micro-tumors in a natural extracellular matrix environment and uses automated 3D imaging to analyze the effects of small molecules and antibodies on tumor development. “The extended range of tumor subtypes and high level of annotation of Charles River’s PDX Compendium enables the selection of the optimum tumor models with the most appropriate mutational profile for in vivo studies,” said Leo Price, CEO and founder of OcellO. “The use of the same PDX tumor cells in OcellO's in vitro 3D culture platform enables pre-screening of tumor models with test compounds in a highly translational high-throughput platform.” In addition to utilizing the Compendium in integrated client relationships, recent tumor model updates have also enhanced scientific presentations. At the 2017 AACR Annual Meeting, a meeting which highlights the advances in cancer science and medicine from institutions all over the world, Charles River presented three posters highlighting the enhancement of certain models for oncology drug discovery: Charles River’s extensive portfolio of oncology products and services, including studies in human xenograft, syngeneic, humanized immunotherapy research models, flow cytometry, and IVIS® imaging services, was strengthened by the acquisition of Oncotest GmbH. Now known as Charles River Discovery Research Services Germany GmbH, the company is a Freiburg, Germany-based organization with a specialization in PDX models with more than 25 years of experience. To address the increasing importance of immuno-oncology, in April 2017 Charles River announced the availability of its triple-immunodeficient mouse model, known as the NCG model. To learn more about Charles River’s oncology research capabilities, visit www.criver.com. Charles River provides essential products and services to help pharmaceutical and biotechnology companies, government agencies and leading academic institutions around the globe accelerate their research and drug development efforts. Our dedicated employees are focused on providing clients with exactly what they need to improve and expedite the discovery, early-stage development and safe manufacture of new therapies for the patients who need them. To learn more about our unique portfolio and breadth of services, visit www.criver.com.


Ding L.,Leibniz Institute for Natural Product Research and Infection Biology | Maier A.,Oncotest GmbH | Fiebig H.-H.,Oncotest GmbH | Gorls H.,Friedrich - Schiller University of Jena | And 4 more authors.
Angewandte Chemie - International Edition | Year: 2011

In-built diversification: Four ansa macrolides, divergolidesa A-D (1-4), with intriguing structures were isolated from a bacterial endophyte of the mangrove tree Bruguiera gymnorrhiza. These compounds are generated by a common biogenesis from a linear precursor that undergoes various reactions to give the multicyclic structures. This remarkable plasticity results in metabolites with different antibacterial and cytotoxic properties. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Ding L.,Leibniz Institute for Natural Product Research and Infection Biology | Maier A.,Oncotest GmbH | Fiebig H.-H.,Oncotest GmbH | Lin W.-H.,Peking University | And 2 more authors.
Organic and Biomolecular Chemistry | Year: 2011

Three novel indolosesquiterpenes, xiamycin B (1b), indosespene (2), and sespenine (3), along with the known xiamycin A (1a) were isolated from the culture broth of Streptomyces sp. HKI0595, a bacterial endophyte of the widespread mangrove tree Kandelia candel. Agar diffusion assays revealed moderate to strong antimicrobial activities against several bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis, while no cytotoxicity against human tumor cell lines was observed. Together with the previously reported oridamycin, the endophyte metabolites represent the first indolosesquiterpenes isolated from prokaryotes. © 2011 The Royal Society of Chemistry.


Kadioglu O.,Johannes Gutenberg University Mainz | Kermani N.S.,University of Hamburg | Kelter G.,Oncotest GmbH | Schumacher U.,University of Hamburg | And 3 more authors.
Biochemical Pharmacology | Year: 2014

Cantharis vesicatoria (blister beetle) is used in Chinese medicine and has been categorized as highly toxic in the Chinese pharmacopeia. In Europe, Cantharis patches have been used since ages to treat various skin-related diseases. We investigated the cytotoxicity of the Cantharis ingredient, cantharidin, in 41 tumor cell lines (Oncotest panel) and compared the results with those of 60 cell lines of the National Cancer Institute, USA. We found profound activity at low micromolar concentrations (log10IC 50 values between -6.980 and 5.009 M). Cantharidin bound to protein phosphatase 2A (PP2A) with higher affinity (-8.12 kcal/mol) than to PP1 (-6.25 kcal/mol) in molecular docking analyses. Using a PCR array for 84 apoptosis genes, cantharidin treatment upregulated gene expression of caspase-1 and nerve growth factor receptor, but downregulated mRNA expression of Bcl-2 like protein 10, Fas ligand, and tumor necrosis factor-α. By using COMPARE analysis of microarray-based transcriptome-wide mRNA expressions, 21 genes were found to significantly correlate with response of 60 tumor cell lines to cantharidin. As shown by hierarchical cluster analysis and chi-squared test, the distribution of cell lines in the dendrogram according to their gene expression profiles predicted sensitivity or resistance to cantharidin (P = 6.482 × 10 -5). The compassionate use of Cantharis patches in two patients suffering from basalioma and Mycosis fungoides, respectively, considerably improved the diseases without signs of toxicity. In conclusion, these results indicate that cantharidin may be a useful candidate to develop novel strategies for cancer therapy. © 2013 Elsevier Inc.


Patent
Oncotest Gmbh and PIRAMAL LIFE science Ltd | Date: 2010-11-15

The present invention provides compounds represented by formula (1): wherein, R_(1), R_(2), R_(3 )and R_(4 )are as defined in the specification, in all their stereoisomeric and tautomeric forms and mixtures thereof in all ratios, and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable polymorphs and prodrugs. The invention also relates to processes for the manufacture of compounds of formula (1) and pharmaceutical compositions containing them. The compounds and the pharmaceutical compositions of the present invention are useful for the treatment of cancer. The present invention further provides a method of treatment of cancer by administering a therapeutically effective amount of the said compound of formula (1) or its pharmaceutical composition, to a mammal in need thereof.


Meyer H.,University of Greifswald | Weidmann H.,University of Greifswald | Weidmann H.,Oncotest GmbH | Lalk M.,University of Greifswald
Microbial Cell Factories | Year: 2013

Background: Bacillus subtilis (B. subtilis) has become widely accepted as a model organism for studies on Gram-positive bacteria. A deeper insight into the physiology of this prokaryote requires advanced studies of its metabolism. To provide a reliable basis for metabolome investigations, a validated experimental protocol is needed since the quality of the analytical sample and the final data are strongly affected by the sampling steps. To ensure that the sample analyzed precisely reflects the biological condition of interest, outside biases have to be avoided during sample preparation.Results: Procedures for sampling, quenching, extraction of metabolites, cell disruption, as well as metabolite leakage were tested and optimized for B. subtilis. In particular the energy status of the bacterial cell, characterized by the adenylate energy charge, was used to evaluate sampling accuracy. Moreover, the results of the present study demonstrate that the cultivation medium can affect the efficiency of the developed sampling procedure.Conclusion: The final workflow presented here allows for the reproducible and reliable generation of physiological data. The method with the highest qualitative and quantitative metabolite yield was chosen, and when used together with complementary bioanalytical methods (i.e., GC-MS, LC-MS and 1H-NMR) provides a solid basis to gather information on the metabolome of B. subtilis. © 2013 Meyer et al.; licensee BioMed Central Ltd.


Smith M.A.,H. Lee Moffitt Cancer Center and Research Institute | Hall R.,H. Lee Moffitt Cancer Center and Research Institute | Fisher K.,H. Lee Moffitt Cancer Center and Research Institute | Haake S.M.,H. Lee Moffitt Cancer Center and Research Institute | And 7 more authors.
Science Signaling | Year: 2015

Strategies to measure functional signaling-associated protein complexes have the potential to augment current molecular biomarker assays, such as genotyping and expression profiling, used to annotate diseases. Aberrant activation of epidermal growth factor receptor (EGFR) signaling contributes to diverse cancers. We used a proximity ligation assay (PLA) to detect EGFR in a complex with growth factor receptor-bound protein 2(GRB2), the major signaling adaptor for EGFR. We used multiple lung cancer cell lines to develop and characterize EGFR:GRB2 PLA and correlated this assay with established biochemical measures of EGFR signaling. In a panel of patient-derived xenografts in mice, the intensity of EGFR:GRB2 PLA correlated with the reduction in tumor size in response to the EGFR inhibitor cetuximab. In tumor biopsies from three cohorts of lung cancer patients, positive EGFR:GRB2 PLA was observed in patients with and without EGFR mutations, and the intensity of EGFR:GRB2 PLA was predictive of overall survival in an EGFR inhibitor-treated cohort. Thus, we established the feasibility of using PLA to measure EGFR signaling-associated protein complexes in patient-based materials, suggesting the potential for similar assays for a broader array of receptor tyrosine kinases and other key signaling molecules. © Copyright 2015 by the American Association for the Advancement of Science; all rights reserved.


Maier A.,Oncotest GmbH | Peille A.-L.,Oncotest GmbH | Vuaroqueaux V.,Oncotest GmbH | Lahn M.,Eli Lilly and Company
Cellular Oncology | Year: 2015

Purpose: The transforming growth factor-beta (TGF-β) signaling pathway is known to play a critical role in promoting tumor growth. Consequently, blocking this pathway has been found to inhibit tumor growth. In order to achieve an optimal anti-tumor effect, however, it remains to be established whether blocking the TGF-β signaling pathway alone is sufficient, or whether the tumor microenvironment plays an additional, possibly synergistic, role.Methods: To investigate the relevance of blocking TGF-β signaling in tumor cells within the context of their respective tissue microenvironments, we treated a panel of patient-derived xenografts (PDX) with the selective TGF-β receptor kinase inhibitor LY2157299 monohydrate (galunisertib) and assessed both the in vitro and in vivo effects.Results: Galunisertib was found to inhibit the growth in an in vitro clonogenic assay in 6.3 % (5/79) of the examined PDX. Evaluation of the expression profiles of a number of genes, representing both canonical and non-canonical TGF-β signaling pathways, revealed that most PDX exhibited expression changes affecting TGF-β downstream signaling. Next, we subjected 13 of the PDX to an in vivo assessment and, by doing so, observed distinct response patterns. These results suggest that, next to intrinsic, also extrinsic or microenvironmental factors can affect galunisertib response. pSMAD2 protein expression and TGF-βRI mRNA expression levels were found to correlate with the in vivo galunisertib effects.Conclusions: From our data we conclude that intrinsic, tumor-dependent TGF-β signaling does not fully explain the anti-tumor effect of galunisertib. Hence, in vivo xenograft models may be more appropriate than in vitro clonogenic assays to assess the anti-tumor activity of TGF-β inhibitors such as galunisertib. © 2015, The Author(s).


Patent
Oncotest Gmbh and PIRAMAL ENTERPRISES Ltd | Date: 2011-08-05

This invention relates to purified compound of formula (1). The invention includes all isomeric forms and all tautomeric forms of the compound of formula (1) and pharmaceutically acceptable salts thereof. The present invention further relates to processes for the production of the compound of formula (1) by fermentation of the fungal strain of sterile mycelium (PM0509732/MTCC5544) and to pharmaceutical compositions containing the compound as active ingredient and its use in medicines for treatment of cancer.


Patent
Oncotest GmbH | Date: 2012-11-28

The present invention relates to pharmaceutical formulations comprising specific hydrazidomycin compounds. Since said hydrazidomycin compounds show cytotoxic activities, the present invention further relates to said hydrazidomycin compounds for use in medicine, in particular in the treatment of proliferative disorders.

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