Objective: To compare the nuclear size of various grades of transitional cell carcinoma (TCC) stained immunohistochemically with the nuclear enzyme topoisomerase II-alpha (topo II-alpha) in bladder urothelial neoplasms.
Study Design: Histologic sections from 53 consecutive papillary bladder neoplasms were stained immunohistochemically for topo II-alpha expression. There were 18 (33.9%) urothelial neoplasms of low malignant potential (UNLMP), 18 (33.9%) low grade urothelial carcinoma (LGUCa), and 17 (32%) with high grade urothelial carcinoma (HGUCa). The histologic slides were photographed at 400 x magnification and then projected on a screen, and the area with stained nuclei was measured.
Results: The cells and nuclei in HGUCa were significantly larger than in LGUCa (P < .05) and UNLMP (P < .01).
Conclusion: Calculation of the area fraction of nuclei in TCC of the bladder stained with topo II-alpha is an additional method of establishing the grade of these tumors.
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J Nat Prod
January 2025
Department of Natural Products, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Airforce Station, Palaj, Gandhinagar 382355, Gujarat, India.
Inspired by our previous efforts in the semisynthetic modification of naturally occurring pyranoacridones, we report the targeted design and semisynthesis of dual inhibitors of HDAC and topoisomerase II α (Topo II α) derived from des--methylacronycine () and noracronycine () pyranoacridone alkaloids. Designed from the clinically approved SAHA, the cytotoxic pyranoacridone nuclei from the alkaloids served as the capping group, while a hydroxamic acid moiety functioned as the zinc-binding group. Out of 16 compounds evaluated in an cytotoxicity assay, KT32 () with noracronycine () as the capping group and five-carbon linker hydroxamic acid side chains showed good cytotoxic activity with IC values of 1.
View Article and Find Full Text PDFFood Chem
February 2025
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, National Engineering Research Center for Functional Food, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, China. Electronic address:
This study investigates the potential of germinated black bean extracts (GBBE) to modulate the activity of topoisomerase IIα (topo IIα), a key enzyme involved in DNA replication and repair, particularly in triple-negative breast cancer (TNBC). Germination significantly elevated the polyphenolic content of black beans, thereby enhancing their antioxidant properties. Molecular docking studies demonstrated a strong interaction between GBBE and the active site of topo IIα, suggesting a possible mechanism for its inhibitory action.
View Article and Find Full Text PDFChem Biol Drug Des
July 2024
División de Ciencias Naturales y Exactas, Departamento de Química, Universidad de Guanajuato, Guanajuato, Mexico.
We have conducted an experimental and computational evaluation of new doxorubicin (4a-c) and β-lapachone (5a-c) analogs. These novel anticancer analogs were previously synthesized, but had not been tested or characterized until now. We have evaluated their antiproliferative and DNA cleavage inhibition properties using breast (MCF-7 and MDA-MB-231) and prostate (PC3) cancer cell lines.
View Article and Find Full Text PDFBioinformation
January 2021
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris - 643001,Tamil Nadu, India.
The enzyme, α-topoisomerase II (α-Topo II), is known to regulate efficiently the topology of DNA. It is highly expressed in rapidly proliferating cells and plays an important role in replication, transcription and chromosome organisation. This has prompted several investigators to pursue α-Topo II inhibitors as anticancer agents.
View Article and Find Full Text PDFRecent Pat Anticancer Drug Discov
March 2022
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York 11439, USA.
Background: DNA topoisomerases are a class of enzymes that play a critical role in fundamental biological processes of replication, transcription, recombination, repair and chromatin remodeling. Amsacrine (m-AMSA), the best-known compound of 9-anilinoacridines series, was one of the first DNA-intercalating agents to be considered a Topoisomerase II inhibitor.
Objectives: A series of sulfur-containing 9-anilinoacridines related to amsacrine were synthesized and evaluated for their anticancer activity.
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