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您的检索式：作者名="Danielle Cicka"
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| 1 | Acquisition of taxane resistance by p53 inactivation in ovarian cancer cells显示文摘Ovarian cancer is one of the most common gynecologic malignancies in women and has a poor prognosis.Taxanes are a class of standard first-line chemotherapeutic agents for the treatment of ovarian cancer.However,tumor-intrinsic and acquired resistance to taxanes poses major challenges to improving clinical outcomes.Hence,there is an urgent clinical need to understand the mechanisms of resistance in order to discover potential biomarkers and therapeutic strategies to increase taxane sensitivity in ovarian cancer.Here,we report the identification of an association between the TP53 status and taxane sensitivity in ovarian cancer cells through complementary experimental and informatics approaches.We found that TP53 inactivation is associated with taxane resistance in ovarian cancer cells,supported by the evidence from(i)drug sensitivity profiling with bioinformatic analysis of large-scale cancer therapeutic response and genomic datasets and(ii)gene signature identification based on experimental isogenic cell line models.Further,our studies revealed TP53-dependent gene expression patterns,such as overexpression of ACSM3,as potential predictive biomarkers of taxane resistance in ovarian cancer.The TP53-dependent hyperactivation of the WNT/β-catenin pathway discovered herein revealed a potential vulnerability to exploit in developing combination therapeutic strategies.Identification of this genotype-phenotype relationship between the TP53 status and taxane sensitivity sheds light on TP53-directed patient stratification and therapeutic discoveries for ovarian cancer treatment. | Changfa Shu Xi Zheng Alafate Wuhafu Danielle Cicka Sean Doyle Qiankun Niu Dacheng Fan Kun Qian Andrey AIvanov Yuhong Du Xiulei Mo Haian Fu | 2022 | Acta Pharmacologica Sinica2022，43，9： | 1 |
| 2 | TMPRSS2 and SARS-CoV-2 SPIKE interaction assay for uHTS显示文摘SARS-CoV-2,the coronavirus that causes the disease COVID-19,has claimed millions of lives over the past 2 years.This demands rapid development of effective therapeutic agents that target various phases of the viral replication cycle.The interaction between host transmembrane serine protease 2(TMPRSS2)and viral SPIKE protein is an important initial step in SARS-CoV-2 infection,offering an opportunity for therapeutic development of viral entry inhibitors.Here,we report the development of a time-resolved fluorescence/Förster resonance energy transfer(TR-FRET)assay for monitoring the TMPRSS2–SPIKE interaction in lysate from cells co-expressing these proteins.The assay was configured in a 384-well-plate format for high-throughput screening with robust assay performance.To enable large-scale compound screening,we further miniaturized the assay into 1536-well ultrahigh-throughput screening(uHTS)format.A pilot screen demonstrated the utilization of the assay for uHTS.Our optimized TR-FRET uHTS assay provides an enabling platform for expanded screening campaigns to discover new classes of small-molecule inhibitors that target the SPIKE and TMPRSS2 protein–protein interaction. | Danielle Cicka Qiankun Niu Min Qui Kun Qian Eric Miller Dacheng Fan Xiulei Mo Andrey AIvanov Stefan GSarafianos Yuhong Du Haian Fu | 2023 | Journal of Molecular Cell Biology2023，15，3： | 0 |
| 3 | Available drugs and supplements for rapid deployment for treatment of COVID-19显示文摘Effective treatment for COVID-19 remains elusive,though urgently needed in the current pandemic.Repurposing marketed therapies may be an effective strategy for finding treatments quickly and recently,in vitro and clinical testing of such therapies against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has skyrocketed.However,not all marketed drugs showing in vitro efficacy could achieve therapeutic concentrations in humans and discernment of drugs that have favorable pharmacokinetic properties can save time and resources for future studies. | Danielle Cicka Vikas P.Sukhatme | 2021 | Journal of Molecular Cell Biology2021，13，3： | 0 |
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