1,720,991 research outputs found
Etoposide and topoisomerase II inhibition for aggressive prostate cancer: Data from a translational study
Background: Etoposide phosphate (VP-16) is a topoisomerase 2 (TOP2) inhibitor that demonstrated activity in patients with metastatic castration-resistant prostate cancer (mCRPC). We investigated the sensitivity of prostate cancer (PCa) cells (LNCaP, 22Rv1, PC3, DU145, PDB and MDB) to VP-16 and the possible relationship between VP-16 activity and TOP2 expression. The activity of VP-16 was compared with that of docetaxel, enzalutamide and olaparib. The prevalence and clinical significance of TOP2 genetic and transcriptomic alterations was also explored in mCRPC. Methods: Cell cultures and crystal violet cell proliferation assays were performed. Specific antibodies were used in western blots analyses of cell protein extracts. Datasets were analyzed in cBioportal. Results: VP-16 was active in all PCa cell lines analyzed and demonstrated increased activity in PC3 and DU145 cells. VP-16 was more cytotoxic compared to the other treatments, except for LNCaP and 22Rv1, which were more sensitive to docetaxel. Maintenance of antiandrogen treatment in MDB and PDB increased sensitivity to VP-16, docetaxel and enzalutamide. TOP2A was found overexpressed in 22Rv1, DU145 and PC3, whereas TOP2B was overexpressed in 22Rv1 and PDB. In the mCRPC datasets analysis, TOP2A mRNA overexpression was associated with worse patients’ prognosis, with the molecular features of neuroendocrine prostate cancer (NEPC) and with lower androgen receptor (AR) score. Patients overexpressing TOP2A mRNA were more likely to harbor RB1 loss. Conclusions: Specific subpopulations of patients with aggressive variant prostate cancer (AVPC) could benefit from VP-16 treatment. TOP2A overexpression, rather than TOP2B, might be a good biomarker to predict response to VP-16
Organization of the lamin scaffold in the internal nuclear matrix of normal and transformed hepatocytes.
The Role of Nuclear Matrix Proteins Binding to Matrix Attachment Regions (MARs) in Prostate Cancer Cell Differentiation
A large SEER- based study of survival trends in patients with de novo metastatic prostate cancer
Real-world survival improvements in patients with newly diagnosed metastatic prostate cancer treated in the United States
Androgen Receptor Activity Is Affected by Both Nuclear Matrix Localization and the Phosphorylation Status of the Heterogeneous Nuclear Ribonucleoprotein K in Anti-Androgen-Treated LNCaP Cells
Effects of the co-administration of Bicalutamide and 4-Hydroxytamoxifen on human prostatic cancer cell line LNCaP
Androgen receptor and heterogeneous nuclear ribonucleoprotein K colocalize in the nucleoplasm and are modulated by bicalutamide and 4-hydroxy-tamoxifen in prostatic cancer cell lines.
Proteomic analysis of the nuclear matrix in the early stages of rat liver carcinogenesis: identification of differentially expressed and MAR-binding proteins.
- …
