Evidence map›Paper›PMID 26238234›Full record

ArticleProstate cancer and prostatic diseases2016

Oral simvastatin administration delays castration-resistant progression and reduces intratumoral steroidogenesis of LNCaP prostate cancer xenografts.

J A Gordon, A Midha, A Szeitz, M Ghaffari, H H Adomat, Y Guo, T L Klassen, E S Guns, K M Wasan, M E Cox

Abstract read
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In one paragraph

Article in Prostate cancer and prostatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.3field-weighted citation impact, top 23% 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

12 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Article
  3. Pleiotropic effects of statins: A focus on cancer.Biochimica et biophysica acta. Molecular basis of disease · 2020
    Review
  4. Article
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  7. Article
  8. LXRs, SHP, and FXR in Prostate Cancer: Enemies orNuclear receptor signaling · 2018
    Review
  9. Article
  10. Article
  11. Article
  12. Targeting intratumoral androgens: statins and beyond.Therapeutic advances in medical oncology · 2016
    Review
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

10 authors at 2 institutions in 1 country.

J A GordonVancouver Prostate Centre, Vancouver Costal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
A MidhaVancouver Prostate Centre, Vancouver Costal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
A SzeitzFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
M GhaffariVancouver Prostate Centre, Vancouver Costal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
H H AdomatVancouver Prostate Centre, Vancouver Costal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
Y GuoVancouver Prostate Centre, Vancouver Costal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
T L KlassenFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
E S GunsVancouver Prostate Centre, Vancouver Costal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
K M WasanFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
M E CoxVancouver Prostate Centre, Vancouver Costal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
University of British Columbia · CAVancouver Coastal Health · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGrowing evidence supports the idea that de novo steroidogenesis has an important role in prostate cancer's progression to the castration-resistant state following androgen deprivation therapy. Therefore, reducing the availability of cholesterol for use as a precursor in androgen synthesis may reduce proliferation and disease progression.

methodsLNCaP xenograft-bearing mice were castrated and administered simvastatin via diet, and tumor volume and PSA concentration were monitored for 8 weeks post castration. Levels of serum and intratumoral androgens along with serum simvastatin and common toxicity markers were measured at end point.

resultsReduced post-castration tumor growth rate in simvastatin-treated mice correlated with delayed time to castration-resistant progression, determined by two serum PSA doublings from post-castration nadir, when compared with xenografts in mice on control diet. At 8 weeks post castration, serum simvastatin levels were comparable to clinically relevant human doses with no evidence of overt muscle or liver toxicity. This suppressed post-castration tumor growth in the simvastatin diet group was correlated with reduced intratumoral testosterone and dihydrotestosterone levels.

conclusionsReduced tumor growth and intratumoral androgen levels observed in simvastatin-treated, castrated mice harboring LNCaP xenograft suggests that suppressing de novo steroidogenesis can delay castration-resistant progression of this tumor model.

Indexed as

Administration, OralAndrogensAnimalsCell Line, TumorCell ProliferationCholesterolDisease ProgressionGene Expression Regulation, NeoplasticHumansMaleMiceProstate-Specific AntigenProstatic Neoplasms, Castration-ResistantSimvastatinXenograft Model Antitumor AssaysAndrogensCholesterolProstate-Specific AntigenSimvastatin

Identifiers

PMID26238234
OpenAlexW1051548727

What OpenQuestion holds

Textmetadata
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.