ArticleInvestigative ophthalmology & visual science2014
Protein kinase C inhibitors sensitize GNAQ mutant uveal melanoma cells to ionizing radiation.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Genetics and RNA Regulation of Uveal Melanoma.Cancers · 2023Review
- Review
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Article
- Measuring the lactate-to-creatine ratio viaCellular & molecular biology letters · 2018Article
- Uveal Melanoma Cell Lines: Where do they come from? (An American Ophthalmological Society Thesis).Transactions of the American Ophthalmological Society · 2016Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
purposeUveal melanoma (UM) tumors require large doses of radiation therapy (RT) to achieve tumor ablation, which frequently results in damage to adjacent normal tissues, leading to vision-threatening complications. Approximately 50% of UM patients present with activating somatic mutations in the gene encoding for G protein αq-subunit (GNAQ), which lead to constitutive activation of downstream pathways, including protein kinase C (PKC). In this study, we investigated the impact of small-molecule PKC inhibitors bisindolylmaleimide I (BIM) and sotrastaurin (AEB071), combined with ionizing radiation (IR), on survival in melanoma cell lines.
methodsCellular radiosensitivity was determined by using a combination of proliferation, viability, and clonogenic assays. Cell-cycle effects were measured by flow cytometry. Transcriptomic and proteomic profiling were performed by quantitative real-time PCR, reverse-phase protein array analysis, and immunofluorescence.
resultsWe found that the PKC inhibitors combined with IR significantly decreased the viability, proliferation, and clonogenic potential of GNAQ(mt), but not GNAQ(wt)/BRAF(mt) cells, compared with IR alone. Combined treatment increased the antiproliferative and proapoptotic effects of IR in GNAQ(mt) cells through delayed DNA-damage resolution and enhanced induction of proteins involved in cell-cycle arrest, cell-growth arrest, and apoptosis.
conclusionsOur preclinical results suggest that combined modality treatment may allow for reductions in the total RT dose and/or fraction size, which may lead to better functional organ preservation in the treatment of primary GNAQ(mt) UM. These findings suggest future clinical trials combining PKC inhibitors with RT in GNAQ(mt) UM warrant consideration.
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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.