Calcusyn User Manual

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Version 2.0 is the analyzer of combined drug effects, able automatically to quantify phenomena such as synergism and inhibition. The use of combined drug treatments is becoming common in the treatment of cancer and AIDS. CalcuSyn performs multiple drug dose-effect calculations using the Median Effect methods described by T-C Chou and P. Talalay (Trends Pharmacol, Sci. 4, 450-454). CalcuSyn can easily be integrated with other software. Data can be entered via the keyboard or file import either into the grid or directly into the analysis engine.

When the grid is used, data can be processed through wizards which make the software easily accessible to new users. Data can be processed both for individual drugs, and for constant-ratio or non-constant-ratio combinations of drugs. CalcuSyn automatically graphs the data and produces reports giving summary statistics on all drugs plus detailed analysis of drug interactions including the Combination Index and EDx (for any value of x). Estimates of accuracy of EDx and CI can be calculated with Monte Carlo simulations or by a highly accurate algebraic estimation algorithm. The plots drawn by CalcuSyn include dose-effect, median-effect, isobolograms and CI-effect. All data and results are easily accessible by mouse-click on the contents tree. CalcuSyn Version 2.0 has Undo and Redo tools.  Ayn rand. There are flexible arrangements for printing of results and graphs and their export to spreadsheets, wordprocessors, and graphics packages. A comprehensive manual is supplied with the software and there is a detailed Help file. These give a thorough account of the theoretical basis of the analysis methods including the statistical treatment of results. CalcuSyn is suitable for the study of drug mixtures.

Comments & References: Suitable for academic labs and pharmaceutical companies. A screenshot and a downloadable demo are. This program can be ordered online. Includes user manual as pdf. Orders outside the United Kingdom, please. Version: 2.0 Price: Single user license: US$300/£175; 5 user license: US$900/£525; 10 user license: US$1500/£875 (all include a manual as pdf file); An additional charge of US$90/£50 is made for supply of a hard copy (CD) if required.

• • 339 Downloads • Abstract Triple negative breast cancers express receptors for gonadotropin-releasing hormone (GnRH) in more than 50% of the cases, which can be targeted with peptidic analogs of GnRH, such as triptorelin. The current study investigates cytotoxic activity of triptorelin as a monotherapy and in treatment combinations with chemotherapeutic agents and inhibitors of the PI3K and the ERK pathways in in vitro models of triple negative breast cancers (TNBC). GnRH receptor expression of TNBC cell lines MDA-MB-231 and HCC1806 was investigated. Cells were treated with triptorelin, chemotherapeutic agents (cisplatin, docetaxel, AEZS-112), PI3K/AKT inhibitors (perifosine, AEZS-129), an ERK inhibitor (AEZS-134), and dual PI3K/ERK inhibitor AEZS-136 applied as single agent therapies and in combinations. MDA-MB-231 and HCC1806 TNBC cells both expressed receptors for GnRH on messenger (m)RNA and protein level and were found sensitive to triptorelin with a respective median effective concentration (EC 50) of 31.21 ± 0.21 and 58.50 ± 19.50.

Synergistic effects occurred when triptorelin was combined with cisplatin. In HCC1806 cells, synergy occurred when triptorelin was applied with PI3K/AKT inhibitors perifosine and AEZS-129. In MDA-MB-231 cells, synergy was observed after co-treatment with triptorelin and ERK inhibitor AEZS-134 and dual PI3K/ERK inhibitor AEZS-136. GnRH receptors on TNBC cells can be used for targeted therapy of these cancers with GnRH agonist triptorelin. Treatment combinations based on triptorelin and PI3K and ERK inhibitors and chemotherapeutic agent cisplatin have synergistic effects in in vitro models of TNBC. If confirmed in vivo, clinical trials based on triptorelin and cisplatin could be quickly carried out, as triptorelin is FDA approved for other indications and known to be well tolerated.