Cell cycle checkpoints play a central role in genomic stability. The human DNA topoisomerase II-binding protein 1 (TopBP1) protein contains eight BRCA1 COOH terminus motifs and shares similarities with Cut5, a yeast checkpoint Rad protein. TopBP1 also shares many features with BRCA1. We report that, when expression of TopBP1 protein is inhibited in BRCA1 mutant cells, mimicking a TopBP1, BRCA1 double-negative condition, the G(2)-M checkpoint is strongly abrogated and apoptosis is increased after ionizing radiation. However, a BRCA1-negative or a TopBP1-negative background resulted in only partial abrogation of the G(2)-M checkpoint. The BRCA1 mutant and TopBP1-reduced condition specifically destroys regulation of the Chk1 kinase but not the Chk2 kinase, suggesting involvement in the ataxia telangiectasia-related pathway. These results indicate that both TopBP1 and BRCA1 specifically regulate the G(2)-M checkpoint, partially compensating each function.
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Clin Cancer Res
January 2025
National Cancer Institute, Bethesda, MD, United States.
Cell cycle checkpoints are stringent quality control mechanisms that regulate cell cycle progression and division. Cancer cells often develop a dependency on the G2/M cell cycle checkpoint to facilitate DNA repair and resolve intrinsic or therapy-induced DNA damage. This dependency leads to therapy resistance, continuous cell division, and disease progression.
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January 2025
The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China.
Background: Hepatocellular carcinoma (HCC) is an inflammation-associated tumor with a dismal prognosis. Immunotherapy has become an important treatment strategy for HCC, as immunity is closely related to inflammation in the tumor microenvironment. Inflammation regulates the expression of programmed death ligand-1 (PD-L1) in the immunosuppressive tumor microenvironment and affects immunotherapy efficacy.
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January 2025
Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.
5-FU is a widely used chemotherapy drug for esophageal carcinomas, but therapy failure has been observed in 5-FU-resistant patients. Overcoming this resistance is a significant challenge in cancer treatment, requiring identifying and targeting important resistance mechanisms. PYGO2 expression is crucial in developing resistance to various chemotherapy drugs.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran.
The current chemotherapy treatments for liver cancer have shown limited effectiveness. Therefore, there is an urgent need to develop new drugs to combat this disease more effectively. This study reports synthesis of cobalt oxide nanoparticles coated with glucose, and conjugated with Ellagic acid.
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February 2025
Department of Chemistry, SRICT-Institute of Science and Research, UPL University of Sustainable Technology, Ankleshwar Valia Road, Vataria 393135, India. Electronic address:
In this study, we aim to detail the design and synthesis of a series of benzothiazole tethered triazole compounds that incorporate acetamide chains, with the purpose of investigating their potential as anticancer agents. The structural integrity of the compounds was confirmed through characterization using H NMR, C NMR, mass spectrometry, and IR spectroscopy. The compounds demonstrated notable cytotoxic effects when tested against a range of cancer cell lines, with a specific inhibition observed in triple-negative breast cancer.
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