Evidence map›Paper›PMID 25516710›Full record

ArticleInternational journal of nanomedicine2014

Nanoparticle delivery of an AKT/PDK1 inhibitor improves the therapeutic effect in pancreatic cancer.

Armando Lucero-Acuña, Justin J Jeffery, Edward R Abril, Raymond B Nagle, Roberto Guzman, Mark D Pagel, Emmanuelle J Meuillet

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of nanomedicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

18 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  12. Polymer nanoparticle-assisted chemotherapy of pancreatic cancer.Therapeutic advances in medical oncology · 2020
    Review
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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

7 authors.

Armando Lucero-AcuñaDepartment of Chemical and Environmental Engineering, University of Arizona, Tucson, AZ, USA.
Justin J JefferyDepartment of Biomedical Engineering, University of Arizona, Tucson, AZ, USA.
Edward R AbrilUniversity of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA ; Department of Pathology, University of Arizona, Tucson, AZ, USA.
Raymond B NagleUniversity of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA ; Department of Pathology, University of Arizona, Tucson, AZ, USA.
Roberto GuzmanDepartment of Chemical and Environmental Engineering, University of Arizona, Tucson, AZ, USA.
Mark D PagelDepartment of Biomedical Engineering, University of Arizona, Tucson, AZ, USA ; University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA ; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA ; Department of Medical Imaging, University of Arizona, Tucson, AZ, USA.
Emmanuelle J MeuilletUniversity of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA ; Department of Molecular and Cell Biology, University of Arizona, Tucson, AZ, USA ; Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA.

Funding

VITAMIN AP30CA023074 · NCI · UNIVERSITY OF ARIZONA · PI Dan Theodorescu · 1985 to 2026
$110.2M
Novel AKT PH domain inhibitors to prevent skin cancerR03CA139503 · NCI · UNIVERSITY OF ARIZONA · PI MEUILLET, EMMANUELLE JOELLE · 2009 to 2010
$146k
NCI NIH HHS CA023074NCI NIH HHS CA139503NCI NIH HHS P30 CA023074NCI NIH HHS R03 CA139503
6 · The paper itself

Abstract

The K-ras mutation in pancreatic cancer can inhibit drug delivery and increase drug resistance. This is exemplified by the therapeutic effect of PH-427, a small molecule inhibitor of AKT/PDK1, which has shown a good therapeutic effect against a BxPC3 pancreatic cancer model that has K-ras, but has a poor therapeutic effect against a MiaPaCa-2 pancreatic cancer model with mutant K-ras. To increase the therapeutic effect of PH-427 against the MiaPaCa-2 pancreatic cancer model with mutant K-ras, we encapsulated PH-427 into poly(lactic-co-glycolic acid) nanoparticles (PNP) to form drug-loaded PH-427-PNP. PH-427 showed a biphasic release from PH-427-PNP over 30 days during studies in sodium phosphate buffer, and in vitro studies revealed that the PNP was rapidly internalized into MiaPaCa-2 tumor cells, suggesting that PNP can improve PH-427 delivery into cells harboring mutant K-ras. In vivo studies of an orthotopic MiaPaCa-2 pancreatic cancer model showed reduced tumor load with PH-427-PNP as compared with treatment using PH-427 alone or with no treatment. Ex vivo studies confirmed the in vivo results, suggesting that PNP can improve drug delivery to pancreatic cancer harboring mutant K-ras.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorDrug CarriersFemaleHumansLactic AcidMiceMice, SCIDNanoparticlesOptical ImagingPancreatic NeoplasmsPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerProtein Kinase InhibitorsProto-Oncogene Proteins c-aktAntineoplastic AgentsDrug CarriersLactic AcidPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerProtein Kinase InhibitorsProto-Oncogene Proteins c-aktAKTbioluminescence imagingdrug deliverynanoparticlespancreatic cancer

Identifiers

PMID25516710
PMCPMC4263440

What OpenQuestion holds

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Registered trials

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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.