ArticleInvestigational new drugs2012
In vitro cytotoxicity of the novel antimyeloma agents perifosine, bortezomib and lenalidomide against different cell lines.
Article in Investigational new drugs, 2012. 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, 9 citations in OpenAlex.
- Phospho-Akt overexpression is prognostic and can be used to tailor the synergistic interaction of Akt inhibitors with gemcitabine in pancreatic cancer.Journal of hematology & oncology · 2017Article
- Plasma and cerebrospinal fluid pharmacokinetics of the Akt inhibitor, perifosine, in a non-human primate model.Cancer chemotherapy and pharmacology · 2015Article
- Cancerous inhibitor of protein phosphatase 2A determines bortezomib-induced apoptosis in leukemia cells.Haematologica · 2013Article
- In vitro effects of perifosine, bortezomib and lenalidomide against hematopoietic progenitor cells from healthy donors.Investigational new drugs · 2012Article
- Perifosine , an oral, anti-cancer agent and inhibitor of the Akt pathway: mechanistic actions, pharmacodynamics, pharmacokinetics, and clinical activity.Expert opinion on drug metabolism & toxicology · 2012Article
- Experimental approaches in the treatment of multiple myeloma.Therapeutic advances in hematology · 2011Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The novel AKT inhibitor perifosine, a synthetic alkylphospholipid, is currently being investigated in clinical trials for the treatment of different hematological and oncological malignancies. The in vitro cytotoxicity of perifosine, bortezomib and lenalidomide against 6 cell lines derived from hematological malignancies was investigated using trypan blue staining, flow cytometry-based detection of activated caspases, Annexin V assays, immunohistochemistry studies (KI-67 and caspase-3 staining) and the immature-myeloid-information (IMI) technique. Perifosine and bortezomib induced concentration- and time-dependent cytotoxicity in all cell lines tested. Perifosine together with bortezomib largely exerted additive or synergistic effects with combination indices ranging from 1.13 to 0.22 for combined efficacies of 25% to 75% after 24-hour incubation. Lenalidomide-triggered cytotoxicity was low in all cell lines tested with any assay (less than 10% compared to the negative control). Finally, perifosine, but not bortezomib or lenalidomide, significantly increased the number of cells detected in the IMI channel. Perifosine and bortezomib- but not lenalidomide- trigger substantial cytotoxicity by caspase activation and mainly act additively or synergistically. The IMI technique might be a useful tool for studying cytotoxicity of agents like perifosine that interact mainly with the cellular membrane.
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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.