Evidence map›Paper›PMID 33946730›Full record

ArticleInternational journal of molecular sciences2021

Procaspase-Activating Compound-1 Synergizes with TRAIL to Induce Apoptosis in Established Granulosa Cell Tumor Cell Line (KGN) and Explanted Patient Granulosa Cell Tumor Cells In Vitro.

Powel Crosley, Anniina Farkkila, Adrianne L Jenner, Chloé Burlot, Olivia Cardinal, Kyle G Potts, Kate Agopsowicz, Marjut Pihlajoki, Markku Heikinheimo, Morgan Craig and 2 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 3 countries.

Powel CrosleyDepartment of Oncology, University of Alberta, Edmonton, AB T6G 2E1, Canada.ORCID 0000-0003-0299-809X
Anniina FarkkilaDepartment of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 8, 00014 Helsinki, Finland.
Adrianne L JennerDepartment of Mathematics and Statistics, Université de Montréal, Montréal, QC H3T 1J4, Canada.ORCID 0000-0001-9103-7092
Chloé BurlotDepartment of Mathematics and Statistics, Université de Montréal, Montréal, QC H3T 1J4, Canada.ORCID 0000-0001-9779-6591
Olivia CardinalDepartment of Mathematics and Statistics, Université de Montréal, Montréal, QC H3T 1J4, Canada.
Kyle G PottsDepartment of Oncology, University of Alberta, Edmonton, AB T6G 2E1, Canada.ORCID 0000-0002-4991-6402
Kate AgopsowiczDepartment of Oncology, University of Alberta, Edmonton, AB T6G 2E1, Canada.
Marjut PihlajokiDepartment of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 8, 00014 Helsinki, Finland.
Markku HeikinheimoChildren's Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 8, 00014 Helsinki, Finland.ORCID 0000-0001-9452-0661
Morgan CraigDepartment of Mathematics and Statistics, Université de Montréal, Montréal, QC H3T 1J4, Canada.ORCID 0000-0003-4852-4770
Yangxin FuDepartment of Oncology, University of Alberta, Edmonton, AB T6G 2E1, Canada.
Mary M HittDepartment of Oncology, University of Alberta, Edmonton, AB T6G 2E1, Canada.
University of Alberta · CAUniversity of Helsinki · FICentre Hospitalier Universitaire Sainte-Justine · CAUniversité de Montréal · CA

Funding

Canada Research Chair in Differential Geometry and Topology naCancer Research Society and the Granulosa Cell Tumour Research Foundation 24194FRQS International Postdoctoral Fellowship naNSERC Discovery Grant RGPIN-2018-04546Sladjana M. Crosley Fund for GCT Research nathe Academy of Finland naThe Sigrid Jusélius Foundation naU.S. Department of Defense W81XWH-16-1-0188Women and Children's Health Research Institute na
6 · The paper itself

Abstract

Granulosa cell tumors (GCT) constitute only ~5% of ovarian neoplasms yet have significant consequences, as up to 80% of women with recurrent GCT will die of the disease. This study investigated the effectiveness of procaspase-activating compound 1 (PAC-1), an activator of procaspase-3, in treating adult GCT (AGCT) in combination with selected apoptosis-inducing agents. Sensitivity of the AGCT cell line KGN to these drugs, alone or in combination with PAC-1, was tested using a viability assay. Our results show a wide range in cytotoxic activity among the agents tested. Synergy with PAC-1 was most pronounced, both empirically and by mathematical modelling, when combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). This combination showed rapid kinetics of apoptosis induction as determined by caspase-3 activity, and strongly synergistic killing of both KGN as well as patient samples of primary and recurrent AGCT. We have demonstrated that the novel combination of two pro-apoptotic agents, TRAIL and PAC-1, significantly amplified the induction of apoptosis in AGCT cells, warranting further investigation of this combination as a potential therapy for AGCT.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsApoptosisBenzoquinonesCarboplatinCaspase 3Cell Line, TumorDeoxycytidineDose-Response Relationship, DrugDrug SynergismEnzyme ActivationFemaleGemcitabineGranulosa Cell TumorHumansHydrazonesIn Vitro Techniques(4-benzylpiperazin-1-yl)acetic acid (3-allyl-2-hydroxybenzylidene)hydrazineBenzoquinonesCarboplatinCASP3 protein, humanCaspase 3DeoxycytidineembelinGemcitabineHydrazonesPiperazinesTNF-Related Apoptosis-Inducing LigandTNFSF10 protein, humancaspase-3GCTmathematical modellingovarian cancerPAC-1

Identifiers

PMID33946730
PMCPMC8124867
OpenAlexW3159440343

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.