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Monitor Drug Efficacy with the In Vivo Link Kit from TopoGEN

Monitor Drug Efficacy with the In Vivo Link Kit from TopoGEN

TopoGEN has developed a kit to clearly demonstrate topo I and II poisoning in the context of the cell.  Use of the In Vivo Link Kit™ provides the researcher unambiguous evidence of drug efficacy within tumor cells. Frequently, when a new drug or compound is identified as a topo targeting agent, the investigator needs to ask basic questions about its entry into the cell.  For example, a positive in vitro hit may not translate into the context of a tumor…

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Topoisomerase II Drug Sensitivity May Be Individually Determined

Topoisomerase II Drug Sensitivity May Be Individually Determined

Effect of a Single Nucleotide Polymorphism in the Murine Double Minute 2 Promoter (SNP309) on the Sensitivity to Topoisomerase II-Targeting Drugs Abstract A single nucleotide polymorphism (SNP) SNP309 (T–>G) in the murine double minute 2 (MDM2) promoter creates a high-affinity Sp1 binding site and increases the expression of MDM2 mRNA and protein. Approximately 40% of the populations harbor at least one variant allele and 12% to 17% are homozygous G/G at codon 309. This MDM2 SNP increases susceptibility to cancer…

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Human Topoisomerase II and Transcription

Human Topoisomerase II and Transcription

DNA topoisomerase IIa is required for RNA polymerase II transcription on chromatin templates Neelima Mondal & Jeffrey D. Parvin Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA Abstract In the nucleus of the cell, core RNA polymerase II (pol II) is associated with a large complex called the pol II holoenzyme (holo-pol)1,2. Transcription by core pol II in vitro on nucleosomal templates is repressed compared with that on templates of histone-free naked DNA3±5. We…

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Topo I Cleavage Complexes and Transcription

Topo I Cleavage Complexes and Transcription

Role for topoisomerase 1 in transcription-associated mutagenesis in yeast High levels of transcription in Saccharomyces cerevisiae are associated with increased genetic instability, which has been linked to DNA damage. Here, we describe a pGAL-CAN1 forward mutation assay for studying transcription-associated mutagenesis (TAM) in yeast. In a wild-type background with no alterations in DNA repair capacity, ≈50% of forward mutations that arise in the CAN1 gene under high-transcription conditions are deletions of 2–5 bp. Furthermore, the deletions characteristic of TAM localize…

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DNA Decatenation Study

DNA Decatenation Study

BRCA1 Participates in DNA Decatenation Zhenkun Lou, Katherine Minter-Dykhouse & Junjie Chen The tumor suppressor BRCA1 has an important function in the maintenance of genomic stability. Increasing evidence suggests that BRCA1 regulates cell cycle checkpoints and DNA repair after DNA damage. However, little is known about its normal function in the absence of DNA damage. Here we show that BRCA1 interacts and colocalizes with topoisomerase IIa in S phase cells. Similar to cells treated with the topoisomerase IIa inhibitor ICRF-193,…

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Topoisomerase I Not Simply Adjusting Genome Topology

Topoisomerase I Not Simply Adjusting Genome Topology

Topoisomerases are well known to be essential for all aspects of DNA function, from replication to repair and particularly in transcription. For this reason, they have for many years been excellent DNA damaging agents that display selectively for tumor cells. A relatively recent finding has come to light that involves topoisomerase I and induction of cellular senescence. Cellular senescence is a form of tumor suppression that puts cells in a more or less permanent proliferative arrest. It is induced by…

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Upcoming Closure May 4-18

Upcoming Closure May 4-18

Our business and shipping facilities will be closed May 4-18 while our staff visits with collaborators in Europe. During this time we will be answering voicemails and emails, so please do continue to contact us. Our offices will be resume our normal product shipping regimen on May 23. Thank you!

Rapid Transport of Novel Topo II Inhibitor into Cancer Cells

Rapid Transport of Novel Topo II Inhibitor into Cancer Cells

F14512, a Potent Antitumor Agent Targeting Topoisomerase II Vectored into Cancer Cells via the Polyamine Transport System Jean-Marc Barret, Anna Kruczynski, Stéphane Vispé, et al. Abstract The polyamine transport system (PTS) is an energy-dependent machinery frequently overactivated in cancer cells with a high demand for polyamines. We have exploited the PTS to selectively deliver a polyamine-containing drug to cancer cells. F14512 combines an epipodophyllotoxin core-targeting topoisomerase II with a spermine moiety introduced as a cell delivery vector. The polyamine tail…

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Doxorubicin: A Preclinical Study

Doxorubicin: A Preclinical Study

Sequencing of Type I Insulin-Like Growth Factor Receptor Inhibition Affects Chemotherapy Response In vitro and In vivo Xianke Zeng,1,2 Deepali Sachdev,2 Hua Zhang,2 Martine Gaillard-Kelly,3 and DouglasYee1,2 Abstract Purpose: The aim of this study was to determine the optimal sequence of combining anti-type I insulin-like growth factor receptor (IGF1R) antibodies with chemotherapeutic drugs in cancer cells in vitro and in vivo. Experimental Design: MCF-7 and LCC6 cells were treated with subcytotoxic concentrations of doxorubicin with or without anti-IGF1R antibodies (scFv-Fc…

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TopoGEN Activity Assays: Topo II Inhibitor Study

TopoGEN Activity Assays: Topo II Inhibitor Study

Thanatop: A Novel 5-Nitrofuran that Is a Highly Active, Cell-Permeable Inhibitor of Topoisomerase II Abstract A series of nitrofuran-based compounds were identified as inhibitors of estrogen signaling in a cell-based, high-throughput screen of a diverse library of small molecules. These highly related compounds were subsequently found to inhibit topoisomerase II in vitro at concentrations similar to that required for the inhibition of estrogen signaling in cells. The most potent nitrofuran discovered is f10-fold more active than etoposide phosphate, a topoisomerase…

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