Kobenhoved, Denmark
Kobenhoved, Denmark

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Trojel-Hansen C.,Rigshospitalet 3731 | Erichsen K.D.,Symbion Inc. | Christensen M.K.,Symbion Inc. | Jensen P.B.,Symbion Inc. | And 2 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2011

Background: Rapidly dividing tumor cells have an increased demand for nutrients to support their characteristic unabated growth; this demand is met by an increased availability of nutrients such as amino acids through vasculogenesis and by the enhanced cellular entry of nutrients through the upregulation of specific transporters. Deprivation of intracellular amino acids or block of amino acid uptake has been shown to be cytotoxic to many established human cancer cell lines in vitro and in human cancer xenograft models. Results: In this paper, we provide evidence that the two small molecule oxyphenisatine analogs TOP001 and TOP216 exert their anti-cancer effect by affecting tumor cell metabolism and inducing intracellular amino acid deprivation, leading to a block of cell proliferation. GCN2-mediated phosphorylation of eIF2α as well as mTOR pathway inhibition supports the above notion. In addition, these novel anti-cancer compounds inhibit DNA and protein synthesis and induce apoptosis in a broad spectrum of cancer cell lines. In vivo, the compounds induce tumor stasis and regression in mouse xenograft models of human breast, prostate, ovarian and pancreatic cancer, both when administered intravenously and orally. Conclusion: In conclusion, these small molecules, built on a 1,3-dihydroindole-2-one scaffold, elicit strong anti-proliferative and cytotoxic activity, and importantly, a strong anti-tumorigenicity is observed in in vivo xenograft models of human breast, ovary, prostate and pancreatic cancers encouraging the translation of this class of compounds into the clinic. © 2010 Springer-Verlag.


Doyle W.M.,Symbion Inc. | Power M.A.,Symbion Inc.
Proceedings of the Annual ISA Analysis Division Symposium | Year: 2010

This paper describes a software approach designed to accelerate process analytical development and deployment by standardizing the interactions with diverse instruments, sampling systems, chemometric packages, and enterprise data systems and by integrating all required functionality at the analyzer level. In addition to the required control and data analysis functions, the system provides local displays in various formats, including statistical information and real-time trend plots, as well as database storage, alarms, and remote communications. It can be implemented on a standard PC or integrated into a dedicated process analytical "appliance" for locked-down deployment.


Kelly J.M.,London School of Hygiene and Tropical Medicine | Taylor M.C.,London School of Hygiene and Tropical Medicine | Horn D.,London School of Hygiene and Tropical Medicine | Loza E.,Latvian Institute of Organic Synthesis | And 3 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2012

A number of hydroxamic acid derivatives which inhibit human histone deacetylases were investigated for efficacy against cultured bloodstream form Trypanosoma brucei. Three out of the four classes tested displayed significant activity. The majority of compounds blocked parasite growth in the submicromolar range. The most potent was a member of the sulphonepiperazine series with an IC 50 of 34 nM. These results identify lead compounds with potential for the development of a novel class of trypanocidal agent. © 2012 Elsevier Ltd. All rights reserved.


Christensen M.K.,Symbion Inc. | Erichsen K.D.,Symbion Inc. | Trojel-Hansen C.,Symbion Inc. | Trojel-Hansen C.,Copenhagen University | And 14 more authors.
Journal of Medicinal Chemistry | Year: 2010

Optimization of the anticancer activity for a class of compounds built on a 1,3-dihydroindole-2-one scaffold was performed. In comparison with recently published derivatives of oxyphenisatin the new analogues exhibited an equally potent antiproliferative activity in vitro and improved tolerability and activity in vivo. The best compounds from this series showed low nanomolar antiproliferative activity toward a series of cancer cell lines (compound (S)-38: IC50 of 0.48 and 2 nM in MCF-7 (breast) and PC3 (prostate), respectively) and potent antitumor effects in well tolerated doses in xenograft models. The racemic compound (RS)-38 showed complete tumor regression at a dose of 20 mg/kg administered iv on days 1 and 7 in a PC3 rat xenograft. © 2010 American Chemical Society.


A process control method that automatically and comprehensively manages the creation, storage and use of electronic records during the operation of a controlled process and for governing and documenting the users that operate the computer systems that are involved in the creation, storage and use of the electronic records. The method controls a process, such as a chemical process, by receiving measurement information relating to the process, applying rules to the received measurement information to determine a desired response, and sending control information to at least one device associated with the process, so as to modify the process. The method maintains the rules, measurements and control activity in transaction logs or audit trails related thereto in a secure database. By providing convenient, centralized control of the process within a secure database, the method enhances compliance with the FDA regulations that permit electronic records to be regarded as the equivalent to paper records under 21 CFR Part 11.


a method for global deployment of analytical methods and merging of data via mobile technology and remote mobile devices, the method comprising: developing analytical methods for quantification and identification to be stored in a relational database and distributed to remote mobile devices; developing execution methods to be stored in a relational database and distributed to remote mobile devices; employing a methodology incorporating gatekeeper applications to ensure full control and traceability in the development, deployment, and use of the analytical methods and the processing and distribution of data and analytical predictions; collecting field data from remote devices to a central relational database for a posterior analysis, model enhancement, and archiving; providing remote distributed access to all stored data including field data and processed data; providing a database methodology that provides for a highly level of security for the transmission of data and the storage of data; and providing a robust networking strategy to accommodate for potentially unreliable and unstable network connections


A process control method that automatically and comprehensively manages the creation, storage and use of electronic records during the operation of a controlled process and for governing and documenting the users that operate the computer systems that are involved in the creation, storage and use of the electronic records. The method controls a process, such as a chemical process, by receiving measurement information relating to the process, applying rules to the received measurement information to determine a desired response, and sending control information to at least one device associated with the process, so as to modify the process. The method maintains the rules, measurements and control activity in transaction logs or audit trails related thereto in a secure database. By providing convenient, centralized control of the process within a secure database, the method enhances compliance with the FDA regulations that permit electronic records to be regarded as the equivalent to paper records under 21 CFR Part 11.


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