Trial reportPloS one2015
Aberrant DNA damage response pathways may predict the outcome of platinum chemotherapy in ovarian cancer.
Trial report in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Sequence-Specific Pharmacokinetic and Pharmacodynamic Phase I/Ib Study of Olaparib Tablets and Carboplatin in Women's Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Retraction Note: Defective DNA repair and chromatin organization in patients with quiescent systemic lupus erythematosus.Arthritis research & therapy · 2025Article
- Article
- DNA Damage Response Network and Intracellular Redox Status in the Clinical Outcome of Patients with Lung Cancer.Cancers · 2024Article
- Relevance of Comet Assay and Phosphorylated-Hsp90α in Cancer Patients' Peripheral Blood Leukocytes as Tools to Assess Cisplatin-based Chemotherapy Clinical Response and Disease Outcome.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2024Article
- Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays.Journal of visualized experiments : JoVE · 2023Article
- GAS6/AXL Inhibition Enhances Ovarian Cancer Sensitivity to Chemotherapy and PARP Inhibition through Increased DNA Damage and Enhanced Replication Stress.Molecular cancer research : MCR · 2022Article
- Role and mechanism of miR-211 in human cancer.Journal of Cancer · 2022Review
- The Effects of Muscle Cell Aging on Myogenesis.International journal of molecular sciences · 2021Article
- The DNA damage response network in the treatment of head and neck squamous cell carcinoma.ESMO open · 2021Article
- A Novel Salt Inducible Kinase 2 Inhibitor, ARN-3261, Sensitizes Ovarian Cancer Cell Lines and Xenografts to Carboplatin.Cancers · 2021Article
- Correction: Aberrant DNA Damage Response Pathways May Predict the Outcome of Platinum Chemotherapy in Ovarian Cancer.PloS one · 2021Article
- Research Progress of PCNA in Reproductive System Diseases.Evidence-based complementary and alternative medicine : eCAM · 2021Review
- DHMEQ enhances the cytotoxic effect of cisplatin and carboplatin in ovarian cancer cell lines.American journal of cancer research · 2021Article
- The exosome-mediated autocrine and paracrine actions of plasma gelsolin in ovarian cancer chemoresistance.Oncogene · 2020Article
- Pre-operative Circulating Plasma Gelsolin Predicts Residual Disease and Detects Early Stage Ovarian Cancer.Scientific reports · 2019Article
- miR-211 facilitates platinum chemosensitivity by blocking the DNA damage response (DDR) in ovarian cancer.Cell death & disease · 2019Article
- hERG1 is involved in the pathophysiological process and inhibited by berberine in SKOV3 cells.Oncology letters · 2019Article
- Inhibition of mTORC1 in pediatric low-grade glioma depletes glutathione and therapeutically synergizes with carboplatin.Neuro-oncology · 2019Article
- Genoprotective effects of gallic acid against cisplatin induced genotoxicity in bone marrow cells of mice.Toxicology research · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian carcinoma (OC) is the most lethal gynecological malignancy. Despite the advances in the treatment of OC with combinatorial regimens, including surgery and platinum-based chemotherapy, patients generally exhibit poor prognosis due to high chemotherapy resistance. Herein, we tested the hypothesis that DNA damage response (DDR) pathways are involved in resistance of OC patients to platinum chemotherapy. Selected DDR signals were evaluated in two human ovarian carcinoma cell lines, one sensitive (A2780) and one resistant (A2780/C30) to platinum treatment as well as in peripheral blood mononuclear cells (PBMCs) from OC patients, sensitive (n = 7) or resistant (n = 4) to subsequent chemotherapy. PBMCs from healthy volunteers (n = 9) were studied in parallel. DNA damage was evaluated by immunofluorescence γH2AX staining and comet assay. Higher levels of intrinsic DNA damage were found in A2780 than in A2780/C30 cells. Moreover, the intrinsic DNA damage levels were significantly higher in OC patients relative to healthy volunteers, as well as in platinum-sensitive patients relative to platinum-resistant ones (all P<0.05). Following carboplatin treatment, A2780 cells showed lower DNA repair efficiency than A2780/C30 cells. Also, following carboplatin treatment of PBMCs ex vivo, the DNA repair efficiency was significantly higher in healthy volunteers than in platinum-resistant patients and lowest in platinum-sensitive ones (t1/2 for loss of γH2AX foci: 2.7±0.5h, 8.8±1.9h and 15.4±3.2h, respectively; using comet assay, t1/2 of platinum-induced damage repair: 4.8±1.4h, 12.9±1.9h and 21.4±2.6h, respectively; all P<0.03). Additionally, the carboplatin-induced apoptosis rate was higher in A2780 than in A2780/C30 cells. In PBMCs, apoptosis rates were inversely correlated with DNA repair efficiencies of these cells, being significantly higher in platinum-sensitive than in platinum-resistant patients and lowest in healthy volunteers (all P<0.05). We conclude that perturbations of DNA repair pathways as measured in PBMCs from OC patients correlate with the drug sensitivity of these cells and reflect the individualized response to platinum-based chemotherapy.
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