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Repair of topoisomerase I-mediated DNA damage.
Publisher Summary This chapter discusses the use of inhibitors of tyrosyl-DNA phosphodiesterase (Tdp1) and Chk1/2 in combination with Topoisomerase I (TopI) inhibitors. TopI is an abundant andExpand
Triptolide: structural modifications, structure-activity relationships, bioactivities, clinical development and mechanisms.
Triptolide, a principal bioactive ingredient of Tripterygium wilfordii Hook F, has attracted extensive exploration due to its unique structure of a diterpenoid triepoxide and multiple biologicalExpand
Chk1 and Chk2 are differentially involved in homologous recombination repair and cell cycle arrest in response to DNA double-strand breaks induced by camptothecins
Camptothecins (CPT) activate S or G2-M arrest and the homologous recombination (HR) repair pathway in tumor cells. In this process, both checkpoint kinases 1 and 2 (Chk1 and Chk2, respectively) areExpand
Defective Mre11-dependent Activation of Chk2 by Ataxia Telangiectasia Mutated in Colorectal Carcinoma Cells in Response to Replication-dependent DNA Double Strand Breaks*
The Mre11·Rad50·Nbs1 (MRN) complex binds DNA double strand breaks to repair DNA and activate checkpoints. We report MRN deficiency in three of seven colon carcinoma cell lines of the NCI AnticancerExpand
Novel indenoisoquinolines NSC 725776 and NSC 724998 produce persistent topoisomerase I cleavage complexes and overcome multidrug resistance.
Camptothecin (CPT) derivatives are effective anticancer drugs, especially against solid tumors. As CPTs are chemically unstable and have clinical limitations, we have synthesized indenoisoquinolinesExpand
Endogenous γ-H2AX-ATM-Chk2 Checkpoint Activation in Bloom's Syndrome Helicase–Deficient Cells Is Related to DNA Replication Arrested Forks
The Bloom syndrome helicase (BLM) is critical for genomic stability. A defect in BLM activity results in the cancer-predisposing Bloom syndrome (BS). Here, we report that BLM-deficient cell lines andExpand
Emerging cancer therapeutic opportunities target DNA-repair systems.
DNA-damaging agents have a central role in non-surgical cancer treatment. The balance between DNA damage and repair determines the final therapeutic consequences. An elevated DNA-repair capacity inExpand
Nonclassic functions of human topoisomerase I: genome-wide and pharmacologic analyses.
The biological functions of nuclear topoisomerase I (Top1) have been difficult to study because knocking out TOP1 is lethal in metazoans. To reveal the functions of human Top1, we have generatedExpand
Tanshinone I inhibits tumor angiogenesis by reducing STAT3 phosphorylation at TYR705 and hypoxia-induced HIF-1α accumulation in both endothelial and tumor cells
Tanshinone I (Tanshinone-1), a major active principle of Salvia miltiorrhiza (Danshen), has been shown to overcome tumor drug resistance and metastasis. Here we report that tanshinone-1 inhibitsExpand
Transcription factor c-Jun activation represses mdr-1 gene expression.
Expression of mdr-1 is complex and highly regulated. Several lines of evidence indirectly suggest that transcription factor c-Jun may negatively regulate human mdr-1 gene expression. We recentlyExpand
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