#Calcusyn synergy how to#
#Calcusyn synergy software#

Results: OSU-2S synergistically enhanced the anti-proliferative effects of sorafenib in the four used HCC cell lines with combination indices <1. The knockdown/over-expression of p53 was used to explain the differential sensitivity of HCC cell lines to sorafenib and/or OSU-2S. PKCОґ knockdown was used to elucidate the role of PKCОґ activation as a mechanism for the synergy. The synergistic interactions were determined by Calcusyn analysis. Methods: The antitumor effects of sorafenib, OSU-2S and their combination were assessed by MTT assay, caspase activation, Western blotting, migration/invasion assays in four different HCC cell lines. OSU-2S, a PKCОґ activator, was selected as a potential candidate anticancer agent to be combined with sorafenib to promote the anti-cancer activity through synergistic interaction. However, the low efficacy and adverse effects at high doses limit the clinical application of sorafenib and strongly recommend its combination with other agents aiming at ameliorating its drawbacks. 5Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan, TaiwanД«ackground: Sorafenib (Nexavar В®) is an FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC).4School of Pharmacy, Chapman University, Irvine, CA, USA.3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.1Sharjah Institute for Medical Research and College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates.Tolba 3,4, Jui-Hsiang Hung 5 and Taleb H. Moreover, pitfalls, limitations, and advantages of using these combinations and Calcusyn/Compusyn are described.Hany A.

#Calcusyn synergy how to#

Here, we describe how combinations can be designed in vitro and how to analyze them using Calcusyn or Compusyn.

#Calcusyn synergy software#

To calculate a CI, the computer software Calcusyn can be used, taking the entire shape of the growth inhibition curve into account for calculating whether a combination is synergistic, additive, or antagonistic. Using this method, a combination index (CI) is calculated from drug cytotoxicity or growth inhibition curves. One of the most widely used ways to evaluate whether a combination is effective is the median-drug effect analysis method. Several attempts have been made to quantitatively measure the doseвЂ“effect relationship of each drug alone and its combinations and to determine whether a given combination would gain a synergistic effect. one drug decreases the side effects of another drug. However, one should realize that an antagonistic action may be desired when toxicity is concerned, i.e. It is essential to test the potency of a combination, before evaluation in the clinic, to prevent antagonistic actions. A combination can be studied by combining the two agents in various different ways, such as simultaneous or sequential combination schedules. one of the agents counteracts the actions of the other. The definition of antagonism is that the combination is less effective than the single agents, e.g. The definition of synergism is that the combination is more effective than each agent separately, e.g., one of the agents augments the actions of the second drug.

However, the study of patterns of possible metabolic and biological interactions in preclinical models, as well as scheduling, should improve the development of most drug combinations. The large majority of combination regimens are being developed empirically and there are few experimental studies designed to explore thoroughly different drug combinations, using appropriate methods of analysis. The primary aim is a mutual enhancement of the therapeutic effects, while other benefits may include decreased side effects and the delay or prevention of drug resistance. Drug combinations are widely used because multiple drugs affect multiple targets and cell subpopulations. Most of the current therapies against cancer, and also those against immune diseases or viral infections, consist of empirically designed combination strategies, combining a variety of therapeutic agents.