ArticleMolecular pharmacology2008
Reduced expression of DNA topoisomerase I in SF295 human glioblastoma cells selected for resistance to homocamptothecin and diflomotecan.
Article in Molecular pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Towards the clinical translation of a novel autophagy inhibitor: Bisaminoquinoline derivative nanoparticles.Biomaterials · 2026Article
- The Kinase Inhibitor GNF-7 Is Synthetically Lethal in Topoisomerase 1-Deficient Ewing Sarcoma.Cancers · 2025Article
- Article
- Herbal Therapies for Cancer Treatment: A Review of Phytotherapeutic Efficacy.Biologics : targets & therapy · 2024Review
- Structure-Activity Relationship of FL118 Platform Position 7 Versus Position 9-Derived Compounds and Their Mechanism of Action and Antitumor Activity.Journal of medicinal chemistry · 2023Article
- Article
- Cellular irinotecan resistance in colorectal cancer and overcoming irinotecan refractoriness through various combination trials including DNA methyltransferase inhibitors: a review.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Article
- Topoisomerase I activity and sensitivity to camptothecin in breast cancer-derived cells: a comparative study.BMC cancer · 2019Article
- Cancer therapeutics using survivin BIRC5 as a target: what can we do after over two decades of study?Journal of experimental & clinical cancer research : CR · 2019Review
- Analysis of topoisomerase I expression and identification of predictive markers for efficacy of topotecan chemotherapy in small cell lung cancer.Thoracic cancer · 2018Article
- Topoisomerase I (Top1): a major target of FL118 for its antitumor efficacy or mainly involved in its side effects of hematopoietic toxicity?American journal of cancer research · 2017Article
- Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their mechanism of action: did we miss something in CPT analogue molecular targets for treating human disease such as cancer?American journal of cancer research · 2017Review
- Microscopic Modes and Free Energies for Topoisomerase I-DNA Covalent Complex Binding with Non-campothecin Inhibitors by Molecular Docking and Dynamics Simulations.Theoretical chemistry accounts · 2013Article
- Article
- Combination of HDAC and topoisomerase inhibitors in small cell lung cancer.Cancer biology & therapy · 2012Article
- Article
- Convection-enhanced delivery of topotecan into a PDGF-driven model of glioblastoma prolongs survival and ablates both tumor-initiating cells and recruited glial progenitors.Cancer research · 2011Article
- Association of SUMO1 and UBC9 genotypes with tumor response in non-small-cell lung cancer treated with irinotecan-based chemotherapy.The pharmacogenomics journal · 2010Article
- DNA topoisomerase I inhibitors: chemistry, biology, and interfacial inhibition.Chemical reviews · 2009Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Homocamptothecins (hCPTs) are a novel class of topoisomerase I (Top1) inhibitors with enhanced chemical stability compared with the currently used camptothecin (CPT) analogs irinotecan and topotecan. The hCPT derivative diflomotecan (BN80915) is currently in clinical trials. We established two resistant human glioblastoma cell lines, SF295/hCPT50 and SF295/BN50, by stepwise exposure of the parental SF295 line to increasing concentrations of hCPT and BN80915, respectively. The two resistant cell lines were 15- to 22-fold resistant to hCPT and BN80915 as well as 7- to 27-fold cross-resistant to other Top1 inhibitors, including CPT, topotecan, and the indenoisoquinolines MJ-III-65 (NSC 706744) and NSC 724998, but sensitive to the topoisomerase II inhibitors mitoxantrone and etoposide. Neither of the resistant cell lines displayed any detectable expression of the three major drug transporters P-glycoprotien, multidrug resistance-associated protein 1, or ATP-binding cassette, subfamily G (WHITE), member 2, as assessed by immunoblot or flow cytometry. Reduced expression of Top1 protein occurred at the transcriptional level in both of the resistant cell lines, consistent with the reduction of Top1 enzyme level as the major contribution to the resistance phenotype in SF295/hCPT50 and SF295/BN50 cells. Treatment of the resistant cell lines with the histone deacetylase inhibitor depsipeptide or the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine alone or concomitantly did not result in re-expression of Top1. Our studies suggest that selection for resistance to hCPT or BN80915 is primarily related to reduced Top1 expression at the transcriptional level, resulting in reduced enzyme levels.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.