Evidence map›Paper›PMID 18723482›Full record

ArticleMolecular cancer therapeutics2008

Androgen receptor inactivation contributes to antitumor efficacy of 17{alpha}-hydroxylase/17,20-lyase inhibitor 3beta-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene in prostate cancer.

Tadas Vasaitis, Aashvini Belosay, Adam Schayowitz, Aakanksha Khandelwal, Pankaj Chopra, Lalji K Gediya, Zhiyong Guo, Hong-Bin Fang, Vincent C O Njar, Angela M H Brodie

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
8.3field-weighted citation impact, top 2% 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

67 citing papers in PubMed, 134 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review

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

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 1 institution in 1 country.

Tadas VasaitisHealth Sciences Facility, University of Maryland, 685 West Baltimore Street, Baltimore, MD 21201, USA.
Aashvini Belosay
Adam Schayowitz
Aakanksha Khandelwal
Pankaj Chopra
Lalji K Gediya
Zhiyong Guo
Hong-Bin Fang
Vincent C O Njar
Angela M H Brodie
University of Maryland, Baltimore · US

Funding

AROMATASE INHIBITORS, BREAST CANCER, &OTHER DISEASESR01CA027440 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI BRODIE, ANGELA M. · 1985 to 2008
$3.2M
AROMATASE AND ANDROGEN INHIBITORS IN PROSTATE CANCERR55CA027440 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI BRODIE, ANGELA M. · 1992 to 1992
–
NCI NIH HHS CA 27440NCI NIH HHS R01 CA027440
6 · The paper itself

Abstract

We previously reported that our novel compound 3beta-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene (VN/124-1) is a potent 17alpha-hydroxylase/17,20-lyase (CYP17) inhibitor/antiandrogen and strongly inhibits the formation and proliferation of human prostate cancer LAPC4 tumor xenografts in severe combined immunodeficient mice. In this study, we report that VN/124-1 and other novel CYP17 inhibitors also cause down-regulation of androgen receptor (AR) protein expression in vitro and in vivo. This mechanism of action seems to contribute to their antitumor efficacy. We compared the in vivo antitumor efficacy of VN/124-1 with that of castration and a clinically used antiandrogen, Casodex, and show that VN/124-1 is more potent than castration in the LAPC4 xenograft model. Treatment with VN/124-1 (0.13 mmol/kg twice daily) was also very effective in preventing the formation of LAPC4 tumors (6.94 versus 2410.28 mm(3) in control group). VN/124-1 (0.13 mmol/kg twice daily) and VN/124-1 (0.13 mmol/kg twice daily) + castration induced regression of LAPC4 tumor xenografts by 26.55% and 60.67%, respectively. Treatments with Casodex (0.13 mmol/kg twice daily) or castration caused significant tumor suppression compared with control. Furthermore, treatment with VN/124-1 caused marked down-regulation of AR protein expression, in contrast to treatments with Casodex or castration that caused significant up-regulation of AR protein expression. The results suggest that VN/124-1 acts by several mechanisms (CYP17 inhibition, competitive inhibition, and down-regulation of the AR). These actions contribute to inhibition of the formation of LAPC4 tumors and cause regression of growth of established tumors. VN/124-1 is more efficacious than castration in the LAPC4 xenograft model, suggesting that the compound has potential for the treatment of prostate cancer.

Indexed as

Androgen Receptor AntagonistsAndrostadienesAntineoplastic AgentsBenzimidazolesBinding, CompetitiveCell Line, TumorDown-RegulationEnzyme InhibitorsHumansMaleProstatic NeoplasmsReceptors, AndrogenSteroid 17-alpha-Hydroxylase3-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-dieneAndrogen Receptor AntagonistsAndrostadienesAntineoplastic AgentsBenzimidazolesEnzyme InhibitorsReceptors, AndrogenSteroid 17-alpha-Hydroxylase

Identifiers

PMID18723482
PMCPMC2643345
OpenAlexW4234452258

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.