Evidence map›Paper›PMID 19470734›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009

Therapeutic Targeting of ATP7B in Ovarian Carcinoma.

Lingegowda S Mangala, Vesna Zuzel, Rosemarie Schmandt, Erik S Leshane, Jyotsna B Halder, Guillermo N Armaiz-Pena, Whitney A Spannuth, Takemi Tanaka, Mian M K Shahzad, Yvonne G Lin and 11 more

Expression of concernOpen access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 79 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 2 pooled it
5.9field-weighted citation impact, top 3% 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

79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 151 citations in OpenAlex.

  1. Pooled it
  2. Overcoming platinum resistance in ovarian carcinoma.Expert opinion on investigational drugs · 2010
    Pooled it
  3. Article
  4. Article
  5. Review
  6. Role of cuproptosis in digestive system tumors (Review).International journal of molecular medicine · 2026
    Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
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  15. Article
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  17. Article
  18. Mechanisms of chemotherapy resistance in ovarian cancer.Cancer drug resistance (Alhambra, Calif.) · 2022
    Review
  19. Review
  20. Review

19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 4 institutions in 2 countries.

Lingegowda S MangalaDepartments of Gynecologic Oncology, Experimental Therapeutics, and Cancer Biology, The University of Texas M. D. Anderson Cancer Center, USA.
Vesna Zuzel
Rosemarie Schmandt
Erik S Leshane
Jyotsna B Halder
Guillermo N Armaiz-Pena
Whitney A Spannuth
Takemi Tanaka
Mian M K Shahzad
Yvonne G Lin
Alpa M Nick
Christopher G Danes
Jeong-Won Lee
Nicholas B Jennings
Pablo E Vivas-Mejia
Judith K Wolf
Robert L Coleman
Zahid H Siddik
Gabriel Lopez-Berestein
Svetlana Lutsenko
Anil K Sood
Gynecologic Oncology Group · USOregon Health & Science University · USBaylor College of Medicine · USThe University of Texas Health Science Center at Houston · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
UNIVERSITY OF TEXAS MD ANDERSON SPORE IN OVARIAN CANCERP50CA083639 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BAST, ROBERT C · 1999 to 2015
$33.0M
Training of Academic Gynecologic OncologistsT32CA101642 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ANIL K SOOD, Kathleen Schmeler · 2005 to 2026
$9.2M
Molecular Mechanisms of ATP-dependent Copper TransportersR01DK071865 · NIDDK · OREGON HEALTH & SCIENCE UNIVERSITY · PI SVETLANA LUTSENKO · 2005 to 2026
$7.9M
Baylor WRHR ProgramK12HD050128 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI BROWN, DALE · 2005 to 2009
$1.8M
Molecular Mechanisms of ATP-Dependent Copper TransportersR56DK071865 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI LUTSENKO, SVETLANA · 2018 to 2018
$539k
Role of Src in Stress-Mediated Progression of Ovarian CancerF31CA126474 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ARMAIZ-PENA, GUILLEROMO N · 2006 to 2009
$108k
NCI NIH HHS CA16672NCI NIH HHS F31 CA126474NCI NIH HHS F31CA126474NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA 083639NCI NIH HHS P50 CA083639NCI NIH HHS T32 CA101642NICHD NIH HHS HD050128NICHD NIH HHS K12 HD050128NIDDK NIH HHS DK071865NIDDK NIH HHS R01 DK071865NIDDK NIH HHS R56 DK071865
6 · The paper itself

Abstract

purposeResistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting a critical platinum resistance gene, ATP7B, using both in vitro and in vivo models. EXPERIMENTAL

designExpression of ATP7A and ATP7B was examined in ovarian cancer cell lines by real-time reverse transcription-PCR and Western blot analysis. ATP7A and ATP7B gene silencing was achieved with targeted small interfering RNA (siRNA) and its effects on cell viability and DNA adduct formation were examined. For in vivo therapy experiments, siRNA was incorporated into the neutral nanoliposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC).

resultsATP7A and ATP7B genes were expressed at higher levels in platinum-resistant cells compared with sensitive cells; however, only differences in ATP7B reached statistical significance. ATP7A gene silencing had no significant effect on the sensitivity of resistant cells to cisplatin, but ATP7B silencing resulted in 2.5-fold reduction of cisplatin IC(50) levels and increased DNA adduct formation in cisplatin-resistant cells (A2780-CP20 and RMG2). Cisplatin was found to bind to the NH(2)-terminal copper-binding domain of ATP7B, which might be a contributing factor to cisplatin resistance. For in vivo therapy experiments, ATP7B siRNA was incorporated into DOPC and was highly effective in reducing tumor growth in combination with cisplatin (70-88% reduction in both models compared with controls). This reduction in tumor growth was accompanied by reduced proliferation, increased tumor cell apoptosis, and reduced angiogenesis.

conclusionThese data provide a new understanding of cisplatin resistance in cancer cells and may have implications for therapeutic reversal of drug resistance.

Indexed as

RNA InterferenceXenograft Model Antitumor AssaysAdenosine TriphosphatasesAnimalsAntineoplastic AgentsApoptosisBinding SitesBlotting, WesternCation Transport ProteinsCell Line, TumorCell ProliferationCell SurvivalCisplatinCopper-Transporting ATPasesDNA AdductsDrug Resistance, NeoplasmAdenosine TriphosphatasesAntineoplastic AgentsATP7A protein, humanATP7B protein, humanCation Transport ProteinsCisplatinCopper-Transporting ATPasesDNA Adducts

Identifiers

PMID19470734
PMCPMC2752981
OpenAlexW2168236445

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.