ArticleJournal of the National Cancer Institute2014
Hyperthermia inhibits recombination repair of gemcitabine-stalled replication forks.
Article in Journal of the National Cancer Institute, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 28 citations in OpenAlex.
- The role of hyperthermia in modern radiation treatment- state of art.Radiation oncology (London, England) · 2025Review
- Calcitriol and hyperthermia potentiate gemcitabine efficacy - A Multifactorial Preclinical Evaluation in Pancreatic and Breast Cancer.Research square · 2025Article
- Efficacy and safety of laparoscopic pancreaticoduodenectomy combined with a modified perioperative intraperitoneal chemotherapy regimen in resectable pancreatic head cancer: a dual-center retrospective cohort study.Frontiers in oncology · 2025Article
- mTORC2 regulates ribonucleotide reductase to promote DNA replication and gemcitabine resistance in non-small cell lung cancer.Neoplasia (New York, N.Y.) · 2021Article
- Mre11 exonuclease activity removes the chain-terminating nucleoside analog gemcitabine from the nascent strand during DNA replication.Science advances · 2020Article
- Radiofrequency deep hyperthermia combined with chemotherapy in the treatment of advanced non-small cell lung cancer.Chinese medical journal · 2019Article
- PARP inhibitors synergize with gemcitabine by potentiating DNA damage in non-small-cell lung cancer.International journal of cancer · 2019Article
- Preclinical In Vitro and In Vivo Evidence of an Antitumor Effect of CX-4945, a Casein Kinase II Inhibitor, in Cholangiocarcinoma.Translational oncology · 2019Article
- Pancreatic adenocarcinoma response to chemotherapy enhanced with non-invasive radio frequency evaluated via an integrated experimental/computational approach.Scientific reports · 2017Article
- Unique heating curves generated by radiofrequency electric-field interactions with semi-aqueous solutions.Applied physics letters · 2017Article
- Effects of hyperthermia on DNA repair pathways: one treatment to inhibit them all.Radiation oncology (London, England) · 2015Review
- A New Imaging Platform for Visualizing Biological Effects of Non-Invasive Radiofrequency Electric-Field Cancer Hyperthermia.PloS one · 2015Article
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 3 institutions in 1 country.
Funding
Abstract
backgroundGemcitabine is a potent nucleoside analogue against solid tumors, but development of drug resistance is a substantial problem. Removal of gemcitabine incorporated into DNA by repair mechanisms may contribute to resistance in chemo-refractory solid tumors. Human hepatocellular carcinoma (HCC) is usually very chemoresistant to gemcitabine.
methodsWe treated HCC in vitro and in vivo (orthotopic murine model with human Hep3B or HepG2 xenografts, 7-10 CB17SCID mice per group) with gemcitabine. The role of homologous recombination repair proteins in repairing stalled replication forks was evaluated with hyperthermia exposure and cell-cycle analysis. The Student t-test was used for two-sample comparisons. Multiple group data were analyzed using one-way analysis of variance. All statistical tests were two-sided.
resultsWe demonstrated that Mre11-mediated homologous recombination repair of gemcitabine-stalled replication forks is crucial to survival of HCC cells. Furthermore, we demonstrated inhibition of Mre11 by an exonuclease inhibitor or concomitant hyperthermia. In orthotopic murine models of chemoresistant HCC, the Hep3B tumor mass with radiofrequency plus gemcitabine treatment (mean ± SD, 180±91mg) was statistically significantly smaller compared with gemcitabine alone (661±419mg, P = .0063).
conclusionsThis study provides mechanistic understanding of homologous recombination inhibiting-strategies, such as noninvasive radiofrequency field-induced hyperthermia, to overcome resistance to gemcitabine in refractory human solid tumors.
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.