Evidence map›Paper›PMID 22753310›Full record

Trial reportThe Prostate2013

Integrated Hedgehog signaling is induced following castration in human and murine prostate cancers.

Eleni Efstathiou, Maria Karlou, Sijin Wen, Anh Hoang, Curtis A Pettaway, Louis L Pisters, Sankar Maity, Patricia Troncoso, Christopher J Logothetis

Open access · greenAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Prostate, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

14 citing papers in PubMed, 18 citations in OpenAlex.

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  13. Hedgehog signaling in prostate cancer and its therapeutic implication.International journal of molecular sciences · 2013
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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

9 authors at 2 institutions in 2 countries.

Eleni EfstathiouDepartment of Clinical Therapeutics, University of Athens Medical School, Athens, Greece.
Maria Karlou
Sijin Wen
Anh Hoang
Curtis A Pettaway
Louis L Pisters
Sankar Maity
Patricia Troncoso
Christopher J Logothetis
The University of Texas MD Anderson Cancer Center · USNational and Kapodistrian University of Athens · GR

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Targeting Tumor Microenvironment-Induced Therapy Resistance in Prostate Cancer Bone MetastasisP50CA140388 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LOGOTHETIS, CHRISTOPHER J., THOMPSON, TIMOTHY CHARLES · 2009 to 2022
$23.4M
Pilot Project ProgramP30ES007784 · NIEHS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI RICHIE, ELLEN R · 1996 to 2011
$16.4M
University of Texas SPORE in Prostate CancerP50CA090270 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LOGOTHETIS, CHRISTOPHER J. · 2001 to 2007
$13.6M
PROSTATE CANCER IN MEXICANS AMERICANS &AFRICAN AMERICANR01CA084964 · NCI · UNIVERSITY OF TEXAS MD ANDERSON CAN CTR · PI STROM, SARA S. · 1999 to 2003
$2.1M
NCI NIH HHS 5 P30 CA016672-35NCI NIH HHS CA84964NCI NIH HHS CA90270NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA090270NCI NIH HHS P50 CA140388NCI NIH HHS R01 CA084964NIEHS NIH HHS ES07784
6 · The paper itself

Abstract

backgroundThe interplay between androgen and Hedgehog (Hh) signaling pathways may be associated with prostate cancer progression and resistance to therapy.

methodsTissue microarrays from prostatectomy specimens were derived from 53 patients treated preoperatively with androgen ablation (AA) with or without chemotherapy, and from 26 stage- and grade-matched controls. A previously characterized androgen-regulated human prostate cancer xenograft was used to conduct parallel murine studies. Expression of markers of interest was determined on both untreated and castrated tumors.

resultsFour-month exposure to AA or AA with chemotherapy led to a uniform increase in Hh signaling as compared to controls, paired with an inverse trend of androgen receptor (AR) and CYP17 expression in clinically derived specimens. Changes in the expression profiles of Hh signaling were observed in the epithelium and stroma, in response to genotoxic stress of androgen ablation and chemotherapy. A reduced expression of KI67 and increased bcl2 expression was observed in the malignant epithelial compartment.

conclusionTo our knowledge, this is the first clinical evidence that Hh signaling is induced by AA or the combination of AA and chemotherapy and, by inference, contributes to castrate-resistant progression of prostate cancer as supported by parallel human and murine studies. These data are in agreement with previous reports that implicate Hh signaling in castrate-resistant progression of prostate cancer. Based on these findings, we are pursuing parallel clinical and murine investigations to determine if Hh signaling inhibition combined with AA will be more effective than AA alone.

Indexed as

OrchiectomyAdenocarcinomaAdultAgedAndrogen AntagonistsAnimalsBiomarkers, TumorCell Line, TumorHedgehog ProteinsHumansMaleMiceMiddle AgedProspective StudiesProstatic NeoplasmsSignal TransductionAndrogen AntagonistsBiomarkers, TumorHedgehog Proteins

Identifiers

PMID22753310
PMCPMC3878994
OpenAlexW2114337481

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.