ArticleCancer cell international2014
In vitro assessment of antitumor activities of the PI3K/mTOR inhibitor GSK2126458.
Article in Cancer cell international, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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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
3 citing papers in PubMed, 4 citations in OpenAlex.
- Omipalisib Inhibits Esophageal Squamous Cell Carcinoma Growth Through Inactivation of Phosphoinositide 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) and ERK Signaling.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Nevospheres from neurocutaneous melanocytosis cells show reduced viability when treated with specific inhibitors of NRAS signaling pathway.Neuro-oncology · 2016Article
- Effects of molecularly targeted therapies on murine thymus: highly selective mTOR inhibitors induce reversible thymic involution.Experimental hematology & oncology · 2015Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUp-regulation of the PI3K/mTOR (phosphatidylinositol-3' kinase/mammalian target of rapamycin) signaling is common in carcinoma. Consistently, targeting these molecules has been shown to halt the growth of many tumors. The main purpose of this study was to develop surrogate biomarkers of the antitumor activity of PI3K/mTOR inhibitors.
methodsFragments from eight tumors were collected immediately after resection in ice-cold RPMI gassed with 95% O2 :5% CO2. Viability was determined by measuring tumor cellular respiration (mitochondrial O2 consumption). The specimens were incubated at 37°C with and without 50 nM GSK2126458 (a highly potent and selective inhibitor of PI3K/mTOR) for 90 min. The tissue was then processed for histology, measurement of intracellular caspase-3 activity (using the caspase-3 substrate N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin), and immunohistochemical detection of the apoptotic biomarkers caspase-3, cytochrome C, and annexin A2.
resultsGSK2126458 induced morphologic changes in four tumors (two invasive ductal carcinomas, one invasive lobular carcinoma, and one ovarian dysgerminoma), intracellular caspase-3 activity in three tumors (two invasive ductal carcinomas and one poorly differentiated signet ring adenocarcinoma of gastric origin), and immunohistochemical evidence of apoptosis in at least four tumors (three invasive ductal carcinomas and one adenocarcinoma of gastric origin). Two tumors (ovarian serous carcinoma and moderately differentiated adenocarcinoma of colorectal origin) demonstrated no treatment effect.
conclusionThese preliminary results demonstrate the feasibility of using in vitro biomarkers for detecting antitumor activities of the rapidly emerging PI3K/mTOR inhibitors.
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