Evidence map›Paper›PMID 24867250›Full record

ArticleMolecular cancer therapeutics2014

Mechanism and efficacy of sub-50-nm tenfibgen nanocapsules for cancer cell-directed delivery of anti-CK2 RNAi to primary and metastatic squamous cell carcinoma.

Gretchen M Unger, Betsy T Kren, Vicci L Korman, Tyler G Kimbrough, Rachel I Vogel, Frank G Ondrey, Janeen H Trembley, Khalil Ahmed

Open access · greenAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 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
2.4field-weighted citation impact, top 11% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Protein Kinase CK2, a Potential Therapeutic Target in Carcinoma ManagementAsian Pacific journal of cancer prevention : APJCP · 2019
    Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Cats, Cancer and Comparative Oncology.Veterinary sciences · 2015
    Review
  15. Evaluation of NIN/RPN12 binding protein inhibits proliferation and growth in human renal cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015
    Article
  16. Article
  17. Article
  18. Article
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

8 authors at 2 institutions in 2 countries.

Gretchen M UngerGeneSegues, Chaska; Departments of.
Betsy T KrenMedicine, Masonic Cancer Center, University of Minnesota; and.
Vicci L KormanGeneSegues, Chaska; Departments of.
Tyler G KimbroughOtolaryngology, and.
Rachel I VogelMasonic Cancer Center, University of Minnesota; and.
Frank G OndreyOtolaryngology, and.
Janeen H TrembleyLaboratory Medicine and Pathology; Masonic Cancer Center, University of Minnesota; and Cellular and Molecular Biochemistry Research Laboratory (151), Minneapolis VA Health Care System, Minneapolis, Minnesota.
Khalil AhmedOtolaryngology, and Laboratory Medicine and Pathology; Masonic Cancer Center, University of Minnesota; and Cellular and Molecular Biochemistry Research Laboratory (151), Minneapolis VA Health Care System, Minneapolis, Minnesota ahmedk@umn.edu.
University of Colorado Cancer Center · USPalmetto Hematology Oncology · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR000114 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2012 to 2015
$35.0M
A Novel Therapeutic Approach for Primary and Metastatic Prostate CancerR01CA150182 · NCI · UNIVERSITY OF MINNESOTA · PI AHMED, KHALIL · 2011 to 2015
$1.4M
In Utero Correction of the OTC Defect in LiverR01DK067436 · NIDDK · UNIVERSITY OF MINNESOTA · PI KREN, BETSY T · 2007 to 2011
$1.4M
Tumor-targeted anti-CK2 RNAi for treatment of HCCR21CA158730 · NCI · UNIVERSITY OF MINNESOTA · PI KREN, BETSY T · 2012 to 2013
$284k
Antisense gene therapy with tumor-targeted nanocapsulesR43CA099366 · NCI · GENESEGUES, INC. · PI UNGER, GRETCHEN M · 2003 to 2003
$245k
Tumor-targeted delivery of siRNA via sub-50 nanometer capsulesR43CA119556 · NCI · GENESEGUES, INC. · PI UNGER, GRETCHEN M · 2006 to 2007
$199k
NCATS NIH HHS UL1 TR000114NCI NIH HHS CA119556NCI NIH HHS CA150182NCI NIH HHS CA158730NCI NIH HHS CA99366NCI NIH HHS HHS-N261-2008-00027/N42CM-2008-00027CNCI NIH HHS P30 CA077598NCI NIH HHS R01 CA150182NCI NIH HHS R21 CA158730NCI NIH HHS R43 CA099366NCI NIH HHS R43 CA119556NIDDK NIH HHS DK067436-05NIDDK NIH HHS R01 DK067436
6 · The paper itself

Abstract

Improved survival for patients with head and neck cancers (HNC) with recurrent and metastatic disease warrants that cancer therapy is specific, with protected delivery of the therapeutic agent to primary and metastatic cancer cells. A further objective should be that downregulation of the intracellular therapy target leads to cell death without compensation by an alternate pathway. To address these goals, we report the utilization of a sub-50-nm tenfibgen (s50-TBG) nanocapsule that delivers RNAi oligonucleotides directed against the essential survival signal protein kinase CK2 (RNAi-CK2) in a cancer cell-specific manner. We have evaluated mechanism and efficacy of using s50-TBG-RNAi-CK2 nanocapsules for therapy of primary and metastatic head and neck squamous cell carcinoma (HNSCC). s50-TBG nanocapsules enter cancer cells via the lipid raft/caveolar pathway and deliver their cargo (RNAi-CK2) preferentially to malignant but not normal tissues in mice. Our data suggest that RNAi-CK2, a unique single-stranded oligonucleotide, co-opts the argonaute 2/RNA-induced silencing complex pathway to target the CK2αα' mRNAs. s50-TBG-RNAi-CK2 inhibited cell growth corresponding with reduced CK2 expression in targeted tumor cells. Treatment of three xenograft HNSCC models showed that primary tumors and metastases responded to s50-TBG-RNAi-CK2 therapy, with tumor shrinkage and 6-month host survival that was achieved at relatively low doses of the therapeutic agent without any adverse toxic effect in normal tissues in the mice. We suggest that our nanocapsule technology and anti-CK2 targeting combine into a therapeutic modality with a potential of significant translational promise.

Indexed as

AnimalsArgonaute ProteinsBase SequenceCarcinoma, Squamous CellCasein Kinase IIFemaleGene Knockdown TechniquesHead and Neck NeoplasmsHumansMembrane MicrodomainsMice, Inbred BALB CMice, NudeNanocapsulesNeoplasm TransplantationPeptide FragmentsRNA InterferenceAGO2 protein, humanArgonaute ProteinsCasein Kinase IINanocapsulesPeptide FragmentsRNA, Small InterferingTenascintenfibgen

Identifiers

PMID24867250
PMCPMC4126856
OpenAlexW2165551720

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.