Evidence map›Paper›PMID 19669229›Full record

ArticleWorld journal of surgery2009

Inhibition of the PI3K pathway suppresses hormonal secretion and limits growth in pheochromocytoma cells.

Joel T Adler, Daniel G Hottinger, Muthusamy Kunnimalaiyaan, Herbert Chen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in World journal of surgery, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 23% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Non-Susceptibility Gene Variants in Head and Neck Paragangliomas.International journal of molecular sciences · 2024
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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

4 authors at 1 institution in 1 country.

Joel T AdlerEndocrine Surgery Research Laboratories, Department of Surgery, University of Wisconsin, H4/722 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA. jtadler@wisc.edu
Daniel G Hottinger
Muthusamy Kunnimalaiyaan
Herbert Chen
University of Wisconsin–Madison · US

Funding

GSK3-beta Signaling in Medullary Thyroid CancerR01CA121115 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI CHEN, HERBERT · 2009 to 2013
$1.5M
Regulating Neuroendocrine Phenotype in CancerR01CA109053 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI CHEN, HERBERT · 2006 to 2010
$1.0M
Phase II Clinical Trial Utilizing Lithium for Patients with Neuroendocrine TumorsR21CA117117 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI CHEN, HERBERT · 2007 to 2008
$467k
NCI NIH HHS R01 CA109053NCI NIH HHS R01-CA109053NCI NIH HHS R01 CA121115NCI NIH HHS R01-CA121115NCI NIH HHS R21 CA117117NCI NIH HHS R21-CA117117
6 · The paper itself

Abstract

backgroundOperative resection is the only curative treatment for pheochromocytomas. Inhibition of the phosphatidylinositol-3 kinase (PI3K)-Akt pathway has been shown to be an effective treatment of neuroendocrine (NE) tumors in vitro. We hypothesized that inhibition of the PI3K-Akt pathway would be a viable strategy to inhibit growth and hormonal secretion in pheochromocytoma cells.

methodsSixteen pheochromocytomas were analyzed for expression of phosphorylated Akt and the NE marker achaete scute complex-like 1 (ASCL1). Pheochromocytoma PC-12 cells were treated with up to 100 microM of the PI3K-specific inhibitor LY294002 for 48 h. Western blot analysis was used to measure phosphorylated Akt, total Akt, ASCL1, chromogranin A (CgA), and markers of apoptosis. Growth was assessed by a methylthiazolyldiphenyl-tetrazolium (MTT) bromide cellular proliferation assay for six days.

resultsHuman pheochromocytomas expressed significant amounts of phosphorylated Akt, and there was a significant correlation between malignant pheochromocytomas and the amount of expressed ASCL1. LY294002 significantly inhibited the PI3K-Akt pathway. Treatment led to a dose-dependent decrease in both ASCL1 and CgA, indicating an alteration in the NE phenotype and hormonal suppression. Treatment decreased cellular proliferation, and cleavage of the apoptotic markers caspase-3 and PARP was observed.

conclusionsHuman pheochromocytoma tumor samples express high levels of phosphorylated Akt. LY294002 effectively inhibits the PI3K-Akt pathway, suppresses NE tumor markers, and decreases cellular proliferation via apoptosis in vitro. Inhibition of the PI3K pathway may represent a new strategy in the treatment of pheochromocytomas.

Indexed as

Phosphoinositide-3 Kinase InhibitorsAdrenal Gland NeoplasmsCell ProliferationChromonesEnzyme InhibitorsHumansMorpholinesPheochromocytomaSignal TransductionTumor Cells, Cultured2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-oneChromonesEnzyme InhibitorsMorpholinesPhosphoinositide-3 Kinase Inhibitors

Identifiers

PMID19669229
PMCPMC3088764
OpenAlexW2013810429

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.