Advances in the theory of combination therapy (1) and development of new targeted drugs are leading to a new emphasis on drug combination experiments. Many studies continue to use the median-effect method of Chou–Talalay (2). However, the median-effect method follows a similar logic to the defunct Scatchard analysis in pharmacology, which has been replaced by nonlinear modeling. Like Scatchard ...

This brief article focuses on two aims: i) To investigate the in vitro pharmaco-dynamic interactions of combining synthetic potent microtubule targeting anticancer agent, Fludelone (FD) with cyto-protective agent, Panaxytriol (PXT) derived from Panax ginseng, and ii) To illustrate step-by-step operation for conducting two-drug combination in vitro using the combination index method, in terms of...

We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70), pifithrin-μ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-μ and cisplatin or oxaliplatin is reported. We have determined, using the Chou-Talalay method, (i) moderate synergi...

Materials and methods CWR22Rv1 cells (a castrate-resistant human PCa cell line) were treated with a polyherbal mixture of botanicals (PHBs) consisting of 10 herbal extracts [1] and we investigated whether inhibition of cell proliferation was linked to the activity of 5’adenosine monophosphate (AMP)activated protein kinase (AMPK), a potential tumor suppressor protein that functions as a central ...

This introduction to the R package mixlow is a (slightly) modified version of Boik and Narasimhan (2010), published in the Journal of Statistical Software. Synergistic and antagonistic drug interactions are important to consider when developing mixtures of anticancer or other types of drugs. Boik, Newman, and Boik (2008) proposed the MixLow method as an alternative to the Median-Effect method o...

man & Villee, 1959; Jarabak, Adams, WilliamsAshman & Talalay, 1962). Talalay & WilliamsAshman (1958) suggested that a steroid dehydrogenase with dual nucleotide specificity is responsible for steroid-dependent transhydrogenation, with one site on the enzyme for which both nucleotides compete. At the stage of enzyme purification reached in the present work it has not been possible to separate NA...

Glioblastoma is the most malignant brain tumor and presents high resistance to chemotherapy radiotherapy. Surgery, radiotherapy with temozolomide are only treatments against this tumor. New targeted therapies, including epigenetic modulators such as 3‑deazaneplanocin A (DZ‑Nep; an EZH2 inhibitor) panobinostat (a histone deacetylase being tested in vitro, together temozolomide. The present study...

The widespread introduction of artemisinin-based combination therapy has contributed to recent reductions in malaria mortality. Combination therapies have a range of advantages, including synergism, toxicity reduction, and delaying the onset of resistance acquisition. Unfortunately, antimalarial combination therapy is limited by the depleting repertoire of effective drugs with distinct target p...

The quinazoline folate analogue raltitrexed (ZD1694; Tomudex) and the camptothecin derivative irinotecan are two new agents showing clinical activity against colorectal cancer. To identify the optimal conditions to achieve synergistic cytotoxicity before the clinical development of their combination, we explored the interactions between ZD1694 and the active metabolite of irinotecan, 7-ethyl-10...