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5-FU is widely used in the treatment of a range of cancers, including CRC, breast and head and neck cancers. Its mechanism of cytotoxicity consists in misincorporation of fluoronucleotides into RNA and DNA but the main toxic effects are mediated by the inhibition of the nucleotide synthetic enzyme thymidylate synthase (TS). 5-FU is an analog of uracil with a fluorine atom. The most studied drug in CRC is the antimetabolite 5-fluorouracil (5-FU), developed over 50 years ago. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.Ĭolorectal cancer (CRC) is the first most prevalent cancer and is the second cause of cancer death in Europe with about 212.000 deaths every year. TCD Pharma is developing the compound TCD717, a ChoKα inhibitor, that is currently in Phase I clinical trials. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: Juan Carlos Lacal is a founder of TCD Pharma and a member of its scientific advisory board but not an employee of the company. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work has been funded by the following grants: Comunidad de Madrid (S-BIO/0280/2006 and S2010/BMD-2326), Ministerio de Ciencia e Innovación (SAF2008-03750, SAF2011-29699, RD06-0020-0016 and RD12/0036/0019) and EU #259737. Received: MaAccepted: ApPublished: June 10, 2013Ĭopyright: © 2013 de la Cueva et al. Lebedeva, Enzo Life Sciences, Inc., United States of America
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(2013) Combined 5-FU and ChoKα Inhibitors as a New Alternative Therapy of Colorectal Cancer: Evidence in Human Tumor-Derived Cell Lines and Mouse Xenografts. ChoKα inhibitors modulate the expression levels of TS and TK1 through inhibition of E2F production, providing a rational for its mechanism of action.Ĭitation: de la Cueva A, Ramírez de Molina A, Álvarez-Ayerza N, Ramos MA, Cebrián A, Pulgar TGd, et al. The combination of 5-FU with ChoKα inhibitors resulted in a synergistic effect in vitro in three different human colon cancer cell lines, and in vivo against human colon xenografts in nude mice. The effects on thymidilate synthase (TS) and thymidine kinase (TK1) levels, two enzymes known to play an essential role in the mechanism of action of 5-FU, were analyzed by western blotting and quantitative PCR analysis. The effect of ChoKα inhibitors in combination with 5-FU as a new alternative for the treatment of colon tumors has been investigated both in vitro in CRC-tumour derived cell lines, and in vivo in mouse xenografts models. The interface is friendly to all users, the response time is good and the computer’s performance is not going to be hindered at all.ChoKα specific inhibitors, MN58b and TCD-717, have demonstrated a potent antitumoral activity both in vitro and in vivo against several tumor-derived cell line xenografts including CRC-derived cell lines.
Calcusyn software#
In conclusion, CalcuSyn is an efficient piece of software which can help people in creating new mixed drug treatment and more effective ones. Experiment details such as title, date, investigator and other notes you deem necessary can be easily provided in a separate pane.īased on a number of user-selected drugs, you can easily create a summary graph, so that you can better view information about your mixed drug treatment experiment. You can add drugs to CalcuSyn manually or with the help of a wizard, so that you can be sure you do not forget to include certain information. File types you can use and other options you can take advantage ofįirst and foremost, you should know it is possible to import data from TXT and XLS files, as well as export it to such documents, so that you can use it in other programs or keep it safe. Nonetheless, it goes without saying that you still require some specialized knowledge in order to get around CalcuSyn. The installation process is over in a jiffy, while the interface you come by encompasses a menu bar, a few buttons, and two panes in which to display a folder structure and selected information.Įxtensive Help contents are provided and thus, it becomes obvious that both power and novice users can find their way around it, without facing any kind of difficulties.
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It can make multiple calculations using the Median Effect methods. CalcuSyn is a software tool whose main purpose is to aid individuals in analyzing mixed drug treatments, a more and more used practice in medicine.