In this paper, we propose a methodology for estimating the execution time of simulations driven by multiscale numerical methods. The methodology explores the idiosyncrasies of multiscale simulators to reduce the uncertainty of predictions. We use the multiscale hybrid-mixed (MHM) finite element method to validate our methodology. We compare our proposed technique with prediction models automatically selected and calibrated by Auto-WEKA. We show that the models obtained with our technique are competitive when compared with the models coming from Auto-WEKA, being interpretable and with much less computational effort during the learning process.
Prostate cancer (PC) is the most common malignant cancer and the second leading cause of cancer‐related deaths in men. Approximately 18.9 out of 100,000 men per year die of prostate cancer. Common treatments such as androgen deprivation therapy (ADT,) surgical castration, and radiation therapy are used to counter PC; however, a proportion of patients relapse within a median of 2‐3 years with castration‐resistant prostate cancer (CRPC). In this study, combined effect of artesunate (ART) with paclitaxel (PTX) on human prostate cancer cell lines – LnCaP (androgen‐ dependent) and PC‐3 (androgen‐independent) were examined. In vitro anti‐proliferative (MTT) assay was used to assess the cytotoxic effects of ART, PTX, and in combination ratios 1:1, 1:2 and 2:1 on LnCaP and PC‐3 after 72‐ hour exposure. The IC50 values of 25.1 μM and 3.98 μM for ART and PXT on PC‐3 while the IC50 values of 2.13 μM and 0.05 μM on LnCaP were observed respectively. The average IC50 values when ART was combines with PXT were 0.499 μM and 0.084 μM on PC‐3 and LnCaP respectively. Overall, this study demonstrates that combining ART with PTX at different combination ratios has more effect on LnCaP than PC‐3 ‐ low IC50. In conclusion, combining ART with PTX displayed cytotoxicity regardless of the type of prostate cancer cell line. This may offer a promising new therapeutic option for the treatment of metastatic hormone‐refractory prostate cancer, aid in reducing cytotoxicity exerted by PTX alone and low prostate cancer mortality rate in men.
Background Prostate cancer is one of the diseases worldwide that causes cancer‐related deaths in men and is the second most common cancer affecting thousands of men each year in the United States behind only lung cancer. Artesunate (ART) is part of the artemisinin drugs for the treatment of malaria. Paclitaxel (PTX) is an anticancer agent that belongs to the Taxane class and is used for the treatment of metastatic hormone‐refractory prostate cancer. Purpose The aim of this study was to examine the effects of combining ART with PTX on human prostate cancer cell lines ‐ LnCAP and PC‐3, normal epithelial prostate cell line RWPE‐1 and observe any morphological change using Scanning Electron Microscope (SEM). Method In vitro anti‐proliferative 3‐(4,5‐Dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) assay was used to assess the effects of ART with PTX on human prostate cancer cell line (LnCaP and PC‐3) and normal prostate cell line (RWPE‐1) after 72‐ and 120 – hour exposure at a concentration range from 1 nm – 100 μM. For the SEM images, cell lines were cultured with thin films of gold, titanium and zinc oxide deposited by magnetron sputtering on silicon substrate at room temperature. Images of samples with and without the drugs were acquired. Results The average cell death observed for both LnCAP and PC‐3 cell lines was 40% and 73% after 72‐ and 120‐ hours incubation with ART and PTX at different combination ratios of 1:1; 1:2 and 2:1 for ART: PTX and 1:1; 1:2 and 2:1 for PTX: ART with concentrations ranging from 1 nm – 100 μM. For normal epithelial prostate cell line, RWPE‐1, the average cell death observed ranged from 0.35% – 23% using the same combination ratios. Cell adhesion was detected on silicon substrates and on thin films of gold, titanium and zinc oxide. Morphological changes were observed when samples were treated with and without drugs. These SEM images were associated with cell lines undergoing apoptosis when compared with control (images with no drugs). Conclusion Although further observations are needed, it appeared that combination of ART with PTX displayed cytotoxicity regardless of whether the prostate cancer cell line is androgen‐sensitive or androgen‐insensitive after 72 and 120 ‐ hour exposure with little or no effect on normal epithelial prostate cell line. Therefore, combination of both drugs may aid in reducing cardio‐toxicity exerted by PTX alone thereby reducing the prostate cancer mortality rate in men. Support or Funding Information Work support by ECSU Mini‐grant and in part by NSF Award# 1818774
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