BackgroundTerpinen-4-ol, a naturally occurring monoterpene is the main bioactive component of tea-tree oil and has been shown to have many biological activities.AimTo study the antitumor effects of terpinen-4-ol and its mechanism of action in prostate and GI malignancies, alone and in combination with chemotherapeutic and biological agents.MethodsTerpinen-4-ol was administrated alone or combined with standard chemotherapy (Oxaliplatin, Fluorouracil, Gemcitabine, Tarceva) and biological agent (Cetuximab). It was also combined with humanized anti-CD24 mAbs (was developed by us). Killing effects were measured qualitatively by light microscopy and quantitatively using the MTT and FACS analysis, following treatment of colorectal, pancreatic, gastric and prostate cancer cells. Terpinen-4-ol effect on tumor development was evaluated in xenograft model.ResultsTerpinen-4-ol induces a significant growth inhibition of colorectal, pancreatic, prostate and gastric cancer cells in a dose-dependent manner (10–90% in 0.005–0.1%). Terpinen-4-ol and various anti-cancer agents (0.2μM oxaliplatin and 0.5μM fluorouracil) demonstrated a synergistic inhibitory effect (83% and 91%, respectively) on cancer cell proliferation. In KRAS mutated colorectal cancer cells, which are resistant to anti-EGFR therapy, combining of terpinen-4-ol with cetuximab (1 μM) resulted in impressive efficacy of 80–90% growth inhibition. Sub-toxic concentrations of terpinen-4-ol potentiate anti-CD24 mAb (150μg/ml)-induced growth inhibition (90%). Considerable reduction in tumor volume was seen following terpinen-4-ol (0.2%) treatment alone and with cetuximab (10mg/kg) (40% and 63%, respectively) as compare to the control group.ConclusionTerpinen-4-ol significantly enhances the effect of several chemotherapeutic and biological agents. The possible molecular mechanism for its activity involves induction of cell-death rendering this compound as a potential anti-cancer drug alone and in combination in the treatment of numerous malignancies. Terpinen-4-ol restores the activity of cetuximab in cancers with mutated KRAS.
A dynamic programming model is formulated for determining surface irrigation schedules over the short term that minimize irrigation labor costs while meeting crop requirements under a limited water supply. This is a relevant problem for a large number of farm operations on the High Plains served by wells tapping the Ogallala Aquifer. The model is capable of solving high‐dimensional problems by a “reaching” forward algorithm that defines a surrogate state space by using binary decision policies rather than by discretization of the actual state variables. Real time use of the short‐term model was simulated for two irrigation seasons, using data from the Northern Colorado Research Demonstration Center near Greeley, Colorado. The model optimized the scheduling of nine field groups divided into a total of 24 fields. An 8% savings in irrigation costs resulted for both years, as compared with conventional scheduling, while maintaining acceptable soil moisture levels.
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