Evidence map›Paper›PMID 26079152›Full record

ArticleBioconjugate chemistry2015

Combination of Nanoparticle-Delivered siRNA for Astrocyte Elevated Gene-1 (AEG-1) and All-trans Retinoic Acid (ATRA): An Effective Therapeutic Strategy for Hepatocellular Carcinoma (HCC).

Devaraja Rajasekaran, Jyoti Srivastava, Kareem Ebeid, Rachel Gredler, Maaged Akiel, Nidhi Jariwala, Chadia L Robertson, Xue-Ning Shen, Ayesha Siddiq, Paul B Fisher and 2 more

Abstract read
In one paragraph

Article in Bioconjugate chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing 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

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

  1. Pooled it
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  8. Oligonucleotide therapies for nonalcoholic steatohepatitis.Molecular therapy. Nucleic acids · 2024
    Review
  9. HCC-Related lncRNAs: Roles and Mechanisms.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

12 authors.

Devaraja Rajasekaran†Department of Human and Molecular Genetics, §Massey Cancer Center; and ∥VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Jyoti Srivastava†Department of Human and Molecular Genetics, §Massey Cancer Center; and ∥VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Kareem Ebeid†Department of Human and Molecular Genetics, §Massey Cancer Center; and ∥VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Rachel Gredler†Department of Human and Molecular Genetics, §Massey Cancer Center; and ∥VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Maaged Akiel†Department of Human and Molecular Genetics, §Massey Cancer Center; and ∥VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Nidhi Jariwala†Department of Human and Molecular Genetics, §Massey Cancer Center; and ∥VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Chadia L Robertson†Department of Human and Molecular Genetics, §Massey Cancer Center; and ∥VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Xue-Ning Shen†Department of Human and Molecular Genetics, §Massey Cancer Center; and ∥VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Ayesha Siddiq†Department of Human and Molecular Genetics, §Massey Cancer Center; and ∥VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Paul B Fisher†Department of Human and Molecular Genetics, §Massey Cancer Center; and ∥VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Aliasger K Salem†Department of Human and Molecular Genetics, §Massey Cancer Center; and ∥VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Devanand Sarkar†Department of Human and Molecular Genetics, §Massey Cancer Center; and ∥VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, Virginia 23298, United States.

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Christopher K Laubenthal · 2000 to 2026
$70.0M
The Role of Monocytes in non-Hodgkin LymphomaP50CA097274 · NCI · UNIVERSITY OF IOWA · PI LENTZ, STEVEN R · 2002 to 2021
$45.7M
Pulmonary Toxicology Facility CoreP30ES005605 · NIEHS · UNIVERSITY OF IOWA · PI Jong Sung Kim · 1990 to 2026
$40.5M
Training Grant in Digestive Diseases and Liver DiseasesT32DK007150 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI SANYAL, ARUN J · 1986 to 2017
$4.2M
Analysis of a novel regulator of hepatocellular carcinomaR01CA138540 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SARKAR, DEVANAND · 2010 to 2014
$1.6M
A novel mediator of obesity associated hepatocellular carcinoma (HCC)R21CA183954 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SARKAR, DEVANAND · 2014 to 2015
$365k
NCI NIH HHS P30 CA086862NCI NIH HHS P50 CA097274NCI NIH HHS P50 CA97274NCI NIH HHS R01 CA138540NCI NIH HHS R21 CA183954NIDDK NIH HHS T32 DK007150NIDDK NIH HHS T32DK007150NIEHS NIH HHS P30 ES005605
6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) is a fatal cancer with no effective therapy. Astrocyte elevated gene-1 (AEG-1) plays a pivotal role in hepatocarcinogenesis and inhibits retinoic acid-induced gene expression and cell death. The combination of a lentivirus expressing AEG-1 shRNA and all-trans retinoic acid (ATRA) profoundly and synergistically inhibited subcutaneous human HCC xenografts in nude mice. We have now developed liver-targeted nanoplexes by conjugating poly(amidoamine) (PAMAM) dendrimers with polyethylene glycol (PEG) and lactobionic acid (Gal) (PAMAM-PEG-Gal) which were complexed with AEG-1 siRNA (PAMAM-AEG-1si). The polymer conjugate was characterized by (1)H-NMR, MALDI, and mass spectrometry; and optimal nanoplex formulations were characterized for surface charge, size, and morphology. Orthotopic xenografts of human HCC cell QGY-7703 expressing luciferase (QGY-luc) were established in the livers of athymic nude mice and tumor development was monitored by bioluminescence imaging (BLI). Tumor-bearing mice were treated with PAMAM-siCon, PAMAM-siCon+ATRA, PAMAM-AEG-1si, and PAMAM-AEG-1si+ATRA. In the control group the tumor developed aggressively. ATRA showed little effect due to high AEG-1 levels in QGY-luc cells. PAMAM-AEG-1si showed significant reduction in tumor growth, and the combination of PAMAM-AEG-1si+ATRA showed profound and synergistic inhibition so that the tumors were almost undetectable by BLI. A marked decrease in AEG-1 level was observed in tumor samples treated with PAMAM-AEG-1si. The group treated with PAMAM-AEG-1si+ATRA nanoplexes showed increased necrosis, inhibition of proliferation, and increased apoptosis when compared to other groups. Liver is an ideal organ for RNAi therapy and ATRA is an approved anticancer agent. Our exciting observations suggest that the combinatorial approach might be an effective way to combat HCC.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCarcinoma, HepatocellularCell Adhesion MoleculesCell ProliferationCombined Modality TherapyGenetic TherapyHumansLiverLiver NeoplasmsMembrane ProteinsMiceMice, Inbred C57BLMice, NudeNanoparticlesAntineoplastic AgentsCell Adhesion MoleculesMembrane ProteinsMTDH protein, humanRNA-Binding ProteinsRNA, Small InterferingTretinoin

Identifiers

PMID26079152
PMCPMC4783168

What OpenQuestion holds

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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.