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Estrogen and Androgen Blockade for Advanced Prostate Cancer in the Era of Precision Medicine
Published in Shaker A. Mousa, Raj Bawa, Gerald F. Audette, The Road from Nanomedicine to Precision Medicine, 2020
Tetsuya Fujimura, Kenichi Takayama, Satoru Takahashi, Satoshi Inoue
SERMs are involved in major therapeutic advancements in clinical practice for breast cancer, osteoporosis, and PC. The first-generation clomiphene, the second-generation toremifene and raloxifene, and the third-generation ospemifene and bazedoxifene have been used in diseases affecting women [73]. SERMs are economical, costing $90 for 50 mg of clomiphene; $1313 for 60 mg of toremifene; and $16 for 60 mg of raloxifene per month, respectively. SERMs are synthetic ligands for ERs that can exhibit either estrogenic or anti-estrogenic effects, depending on the tissue type [73]. SERMs have tissue-specific agonist–antagonist activity [74]. For example, raloxifene exhibited diverse activities via ER depending on ERα or ERβ expression in the target organ [75]. When ERE-luciferase (ERE-LUC) and either ERα or ERβ were co-transfected into HEK 293 cells, toremifene acted as a potent antagonist of the 17β-estradiol-stimulated transactivation of ERα (at 1 µM) and ERβ (at 5 µM), respectively [74]. In contrast, toremifene (0.1 µM) served as a potent antagonist of ERα (95% inhibition), but not of ERβ (20% inhibition). Thus, toremifene is a more selective antagonist of ERα, the activation of which is implicated in prostate epithelial growth, than of ERβ [74]. Toremifene significantly reduced PC incidence in a transgenic adenocarcinoma of mouse prostate model [76]. Toremifene treatment resulted in a significant reduction in prostate tumor growth and PC3M (a human PC cell line) proliferation, expressing ERα [77].
Estrogen and Androgen Blockade for Advanced Prostate Cancer in the Era of Precision Medicine
Published in Shaker A. Mousa, Raj Bawa, Gerald F. Audette, The Road from Nanomedicine to Precision Medicine, 2019
Tetsuya Fujimura, Kenichi Takayama, Satoru Takahashi, Satoshi Inoue
SERMs are involved in major therapeutic advancements in clinical practice for breast cancer, osteoporosis, and PC. The first-generation clomiphene, the second-generation toremifene and raloxifene, and the third-generation ospemifene and bazedoxifene have been used in diseases affecting women [73]. SERMs are economical, costing $90 for 50 mg of clomiphene; $1313 for 60 mg of toremifene; and $16 for 60 mg of raloxifene per month, respectively. SERMs are synthetic ligands for ERs that can exhibit either estrogenic or anti-estrogenic effects, depending on the tissue type [73]. SERMs have tissue-specific agonist–antagonist activity [74]. For example, raloxifene exhibited diverse activities via ER depending on ERα or ERβ expression in the target organ [75]. When ERE-luciferase (ERE-LUC) and either ERα or ERβ were co-transfected into HEK 293 cells, toremifene acted as a potent antagonist of the 17β-estradiol-stimulated transactivation of ERα (at 1 µM) and ERβ (at 5 µM), respectively [74]. In contrast, toremifene (0.1 µM) served as a potent antagonist of ERα (95% inhibition), but not of ERβ (20% inhibition). Thus, toremifene is a more selective antagonist of ERα, the activation of which is implicated in prostate epithelial growth, than of ERβ [74]. Toremifene significantly reduced PC incidence in a transgenic adenocarcinoma of mouse prostate model [76]. Toremifene treatment resulted in a significant reduction in prostate tumor growth and PC3M (a human PC cell line) proliferation, expressing ERα [77].
Evaluation of Food and Food Contaminants
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 5, 2017
William J. Rea, Kalpana D. Patel
Receptor ligands can have diverse outcomes after receptor binding, including agonism; antagonism, acting as an inverse agonist, as partial agonist/antagonist, or as a mixed agonist–antagonist, and as modulators. Along with the nature of the ligand, the outcome can be driven by tissue type and activation status. Again, serial dilution of a low-dose incitant can trigger or ameliorate the effects on the endocrine system.
Machine learning models for predicting endocrine disruption potential of environmental chemicals
Published in Journal of Environmental Science and Health, Part C, 2018
Marco Chierici, Marco Giulini, Nicole Bussola, Giuseppe Jurman, Cesare Furlanello
Supported by accuracy improvements reported for autoencoder architectures trained on the ToxCast invitrodb dataset,22 we aim in particular at extending the application of the QSAR data-driven approach to deep learning architectures to improve sensitivity of CERAPP tasks. Specifically, the CERAPP assessed the application of predictive modeling to evaluate the binding interactions of environmental chemicals to the ligand-binding domain of human ER from in vitro high-throughput screening (HTS) assay data. These interactions are differentiated into three classes: agonist, antagonist and binding. The CERAPP has defined a training set of 5031 compounds (1677 per class) and the “Literature Evaluation set” (6319, 6539, and 7283, respectively, for agonist, antagonist, and binding) labeled as positive or negative. The data defines three distinct learning tasks, which are tackled by ML4Tox with a deep multilayer network, a linear SVM and a Gaussian SVM, respectively, yielding superior performances over those published. We present here the general architecture of the ML4Tox framework, its main methods and experimental application to the CERAPP tasks, finally discussing the potential for the future development of deep learning architectures in predictive toxicology.
Force control of twisted and coiled polymer actuators via active control of electrical heating and forced convective liquid cooling
Published in Advanced Robotics, 2018
In general, because the artificial muscles only produce output forces to the single direction, a pair of the artificial muscles are used antagonistically on each joint to produce both positive and negative forces or torques. In this section, we introduce the agonist–antagonist actuation system of TCPs and extend our control methodology of the single TCP to the agonist–antagonist TCPs.
Anthropomorphic musculoskeletal 10 degrees-of-freedom robot arm driven by pneumatic artificial muscles
Published in Advanced Robotics, 2018
Arne Hitzmann, Hiroaki Masuda, Shuhei Ikemoto, Koh Hosoda
A possible alternative actuation scheme is the use of virtual agonist-antagonist mechanisms, such as introduced by [26]. Their use could eradicate the current shortcomings of PAMs, as soon as complex high DoF systems using such devices can be developed.