Evidence map›Paper›PMID 18719367›Full record

ArticleCancer biology & therapy2008

Downregulation of KSR1 in pancreatic cancer xenografts by antisense oligonucleotide correlates with tumor drug uptake.

Jianjun Zhang, Mohammad Zafrullah, Xia Yang, Xianglei Yin, Zhigang Zhang, Zvi Fuks, Richard Kolesnick

Open access · hybridAbstract read
In one paragraph

Article in Cancer biology & therapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.3field-weighted citation impact, top 40% 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

9 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. KSR as a therapeutic target for Ras-dependent cancers.Expert opinion on therapeutic targets · 2017
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. 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

7 authors at 1 institution in 1 country.

Jianjun ZhangLaboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Mohammad Zafrullah
Xia Yang
Xianglei Yin
Zhigang Zhang
Zvi Fuks
Richard Kolesnick
Memorial Sloan Kettering Cancer Center · US

Funding

Targeting KSR to Treat Pancreatic CancerR01CA042385 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI KOLESNICK, RICHARD N · 1986 to 2010
$3.4M
NCI NIH HHS R01 CA042385NCI NIH HHS R01 CA42385
6 · The paper itself

Abstract

While antisense oligonucleotide (AS-ODN) technology holds promise for the treatment of cancer, to date there have been no clinical successes. Unfortunately, current assays are not sufficiently sensitive to measure tissue ODN levels. Hence it has not been possible to ascertain whether treatment failures result from failure of drug delivery. To investigate the relationship between drug uptake and therapeutic effect, we developed an ultrasensitive noncompetitive hybridization-ligation enzyme-linked immunosorbent assay (NCHL-ELISA) to quantify Kinase Suppressor of Ras1 (KSR1) AS-ODN drug uptake in plasma and tumor tissues. In mice harboring PANC-1 pancreatic cancer xenografts and continuously infused with AS-ODN, our ELISA detects plasma and tumor KSR1 AS-ODN levels over an extended range, from 0.05 nM to 20 nM. Using this sensitive assay, we demonstrate that KSR1 repression in pancreatic cancer xenografts correlates highly with AS-ODN uptake into tumor tissues. In contrast, plasma drug levels do not correlate with tumor drug content or target downregulation. These studies indicate the efficacy of our ELISA, and suggest that tumor biopsy material will need to be procured to estimate the potential of this antisense technology.

Indexed as

AnimalsDose-Response Relationship, DrugDown-RegulationEnzyme-Linked Immunosorbent AssayHumansMaleMiceMice, NudeOligonucleotides, AntisensePancreatic NeoplasmsProtein KinasesSensitivity and SpecificityXenograft Model Antitumor AssaysKSR-1 protein kinaseOligonucleotides, AntisenseProtein Kinases

Identifiers

PMID18719367
PMCPMC2576298
OpenAlexW2070981912

What OpenQuestion holds

Textmetadata
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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.