In vitro 3D cancer spheroids (tumoroids) exhibit a drug resistance profile similar to that found in solid tumors. 3D spheroid culture methods recreate more physiologically relevant microenvironments for cells. Therefo...In vitro 3D cancer spheroids (tumoroids) exhibit a drug resistance profile similar to that found in solid tumors. 3D spheroid culture methods recreate more physiologically relevant microenvironments for cells. Therefore, these models are more appropriate for cancer drug screening. We have recently developed a protocol for MCF-7 cell spheroid culture, and used this method to test the effects of different types of drugs on this estrogen-dependent breast cancer cell spheroid. Our results demonstrated that MCF-7 cells can grow spheroid in medium using a low attachment plate. We managed to grow one spheroid in each well, and the spheroid can grow over a month, the size of the spheroid can grow over a hundred times in volume. Our targeted drug experimental results suggest that estrogen sulfotransferase, steroid sulfatase, and G protein-coupled estrogen receptor may play critical roles in MCF-7 cell spheroid growth, while estrogen receptors α and β may not play an essential role in MCF-7 spheroid growth. Organoids are the miniatures of in vivo tissues and reiterate the in vivo microenvironment of a specific organ, best fit for the in vitro studies of diseases and drug development. Tumoroid, developed from cancer cell lines or patients’ tumor tissue, is the best in vitro model of in vivo tumors. 3D spheroid technology will be the best future method for drug development of cancers and other diseases. Our reported method can be developed clinically to develop personalized drugs when the patient’s tumor tissues are used to develop a spheroid culture for drug screening.展开更多
Infectious pandemics result in hundreds and millions of deaths,notable examples of the Spanish Flu,the Black Death and smallpox.The current pandemic,caused by SARS-CoV-2(severe acute respiratory syndrome coronavirus 2...Infectious pandemics result in hundreds and millions of deaths,notable examples of the Spanish Flu,the Black Death and smallpox.The current pandemic,caused by SARS-CoV-2(severe acute respiratory syndrome coronavirus 2),is unprecedented even in the historical term of pandemics.The unprecedentedness is featured by multiple surges,rapid identification of therapeutic options and accelerated development of vaccines.Remdesivir,originally developed for Ebola viral disease,is the first treatment of COVID-19(Coronavirus disease 2019)approved by the United States Food and Drug Administration.As demonstrated by in vitro and preclinical studies,this therapeutic agent is highly potent with a broad spectrum activity against viruses from as many as seven families even cross species.However,randomized controlled trials have failed to confirm the efficacy and safety.Remdesivir improves some clinical signs but not critical parameters such as mortality.This antiviral agent is an ester/phosphorylation prodrug and excessive hydrolysis which increases cellular toxicity.Remdesivir is given intravenously,leading to concentration spikes and likely increasing the potential of hydrolysis-based toxicity.This review has proposed a conceptual framework for improving its efficacy and minimizing toxicity not only for the COVID-19 pandemic but also for future ones caused by remdesivir-sensitive viruses.展开更多
文摘In vitro 3D cancer spheroids (tumoroids) exhibit a drug resistance profile similar to that found in solid tumors. 3D spheroid culture methods recreate more physiologically relevant microenvironments for cells. Therefore, these models are more appropriate for cancer drug screening. We have recently developed a protocol for MCF-7 cell spheroid culture, and used this method to test the effects of different types of drugs on this estrogen-dependent breast cancer cell spheroid. Our results demonstrated that MCF-7 cells can grow spheroid in medium using a low attachment plate. We managed to grow one spheroid in each well, and the spheroid can grow over a month, the size of the spheroid can grow over a hundred times in volume. Our targeted drug experimental results suggest that estrogen sulfotransferase, steroid sulfatase, and G protein-coupled estrogen receptor may play critical roles in MCF-7 cell spheroid growth, while estrogen receptors α and β may not play an essential role in MCF-7 spheroid growth. Organoids are the miniatures of in vivo tissues and reiterate the in vivo microenvironment of a specific organ, best fit for the in vitro studies of diseases and drug development. Tumoroid, developed from cancer cell lines or patients’ tumor tissue, is the best in vitro model of in vivo tumors. 3D spheroid technology will be the best future method for drug development of cancers and other diseases. Our reported method can be developed clinically to develop personalized drugs when the patient’s tumor tissues are used to develop a spheroid culture for drug screening.
基金supported by National Institutes of Health Grants R01 EB018748,R21 Al153031University of Cincinnati Cancer Center(Yan,B).
文摘Infectious pandemics result in hundreds and millions of deaths,notable examples of the Spanish Flu,the Black Death and smallpox.The current pandemic,caused by SARS-CoV-2(severe acute respiratory syndrome coronavirus 2),is unprecedented even in the historical term of pandemics.The unprecedentedness is featured by multiple surges,rapid identification of therapeutic options and accelerated development of vaccines.Remdesivir,originally developed for Ebola viral disease,is the first treatment of COVID-19(Coronavirus disease 2019)approved by the United States Food and Drug Administration.As demonstrated by in vitro and preclinical studies,this therapeutic agent is highly potent with a broad spectrum activity against viruses from as many as seven families even cross species.However,randomized controlled trials have failed to confirm the efficacy and safety.Remdesivir improves some clinical signs but not critical parameters such as mortality.This antiviral agent is an ester/phosphorylation prodrug and excessive hydrolysis which increases cellular toxicity.Remdesivir is given intravenously,leading to concentration spikes and likely increasing the potential of hydrolysis-based toxicity.This review has proposed a conceptual framework for improving its efficacy and minimizing toxicity not only for the COVID-19 pandemic but also for future ones caused by remdesivir-sensitive viruses.
