ArticleOncotarget2018
Development of a quantitative pharmacodynamic assay for apoptosis in fixed tumor tissue and its application in distinguishing cytotoxic drug-induced DNA double strand breaks from DNA double strand breaks associated with apoptosis.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Macrophage Subsets and Death Are Responsible for Atherosclerotic Plaque Formation.Frontiers in immunology · 2022Pooled it
- Phase I trial of the combination of bortezomib and clofarabine in adults with refractory tumors.Cancer chemotherapy and pharmacology · 2026Article
- Safety and Tolerability of Berzosertib, an Ataxia-Telangiectasia-Related Inhibitor, and Veliparib, an Oral Poly (ADP-ribose) Polymerase Inhibitor, in Combination With Cisplatin in Patients With Refractory Solid Tumors.JCO precision oncology · 2025Article
- Phase 1 studies of the indenoisoquinolines LMP776 and LMP744 in patients with solid tumors and lymphomas.Cancer chemotherapy and pharmacology · 2025Article
- Metabolic imaging distinguishes ovarian cancer subtypes and detects their early and variable responses to treatment.Oncogene · 2025Article
- Development of Mouse-Tumor Model Using Prostate Cancer (PC3) Cell Line for High-Intensity Focused Ultrasound (HIFU) Ablation.Prostate cancer · 2025Article
- Article
- Profiling DNA damage in 3D Histology Samples.Medical optical imaging and virtual microscopy image analysis : first International Workshop, MOVI 2022, held in conjunction with MICCAI 2022, Singapore, September 18, 2022, Proceedings. MOVI (Workshop) (1st : 2022 : Singapore) · 2022Article
- ROADMAPS: An Online Database of Response Data, Dosing Regimens, and Toxicities of Approved Oncology Drugs as Single Agents to Guide Preclinical In Vivo Studies.Cancer research · 2022Article
- DNA damage response proteins in canine cancer as potential research targets in comparative oncology.Veterinary and comparative oncology · 2022Review
- IAP and HDAC inhibitors interact synergistically in myeloma cells through noncanonical NF-κB- and caspase-8-dependent mechanisms.Blood advances · 2021Article
- Safety, Antitumor Activity, and Biomarker Analysis in a Phase I Trial of the Once-daily Wee1 Inhibitor Adavosertib (AZD1775) in Patients with Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Smac-mimetic enhances antitumor effect of standard chemotherapy in ovarian cancer models via Caspase 8-independent mechanism.Cell death discovery · 2021Article
- Benzothiazole derivative bearing amide moiety induces p53-mediated apoptosis in HPV16 positive cervical cancer cells.Investigational new drugs · 2020Article
- Evaluation of Pharmacodynamic Responses to Cancer Therapeutic Agents Using DNA Damage Markers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- NCI Comparative Oncology Program Testing of Non-Camptothecin Indenoisoquinoline Topoisomerase I Inhibitors in Naturally Occurring Canine Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Wee1 Inhibitor AZD1775 Combined with Cisplatin Potentiates Anticancer Activity against Gastric Cancer by Increasing DNA Damage and Cell Apoptosis.BioMed research international · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
DNA double strand breaks (DSBs) induced by cancer therapeutic agents can lead to DNA damage repair or persistent DNA damage, which can induce apoptotic cell death; however, apoptosis also induces DSBs independent of genotoxic insult. γH2AX is an established biomarker for DSBs but cannot distinguish between these mechanisms. Activated cleaved caspase-3 (CC3) promotes apoptosis by enhancing nuclear condensation, DNA fragmentation, and plasma membrane blebbing. Here, we describe an immunofluorescence assay that distinguishes between apoptosis and drug-induced DSBs by measuring coexpression of γH2AX and membrane blebbing-associated CC3 to indicate apoptosis, and γH2AX in the absence of CC3 blebbing to indicate drug-induced DNA damage. These markers were examined in xenograft models following treatment with topotecan, cisplatin, or birinapant. A topotecan regimen conferring tumor regression induced tumor cell DSBs resulting from both apoptosis and direct DNA damage. In contrast, a cisplatin regimen yielding tumor growth delay, but not regression, resulted in tumor cell DSBs due solely to direct DNA damage. MDA-MB-231 xenografts exposed to birinapant, which promotes apoptosis but does not directly induce DSBs, exhibited dose-dependent increases in colocalized γH2AX/CC3 blebbing in tumor cells. Clinical feasibility was established using formalin-fixed, paraffin-embedded biopsies from a canine cancer clinical trial; γH2AX/CC3 colocalization analysis revealed apoptosis induction by two novel indenoisoquinoline topoisomerase I inhibitors, which was consistent with pathologist-assessed apoptosis and reduction of tumor volume. This assay is ready for use in clinical trials to elucidate the mechanism of action of investigational agents and combination regimens intended to inflict DNA damage, apoptotic cell death, or both.
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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.