Evidence map›Paper›PMID 28073588›Full record

ArticleSurgery2017

Overexpression of cytochrome P450 2A6 in adrenocortical carcinoma.

Timothy D Murtha, Taylor C Brown, Jill C Rubinstein, Felix Haglund, C Christofer Juhlin, Catharina Larsson, Reju Korah, Tobias Carling

Open access · greenAbstract read
In one paragraph

Article in Surgery, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

4 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Human Orphan Cytochromes P450: An Update.Current drug metabolism · 2022
    Article
  3. Review
  4. 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

8 authors at 2 institutions in 1 country.

Timothy D MurthaYale Department of Surgery & Yale Endocrine Neoplasia Laboratory, Yale School of Medicine, New Haven, CT.
Taylor C BrownYale Department of Surgery & Yale Endocrine Neoplasia Laboratory, Yale School of Medicine, New Haven, CT.
Jill C RubinsteinYale Department of Surgery & Yale Endocrine Neoplasia Laboratory, Yale School of Medicine, New Haven, CT.
Felix HaglundDepartment of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
C Christofer JuhlinDepartment of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Catharina LarssonDepartment of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Reju KorahYale Department of Surgery & Yale Endocrine Neoplasia Laboratory, Yale School of Medicine, New Haven, CT.
Tobias CarlingYale Department of Surgery & Yale Endocrine Neoplasia Laboratory, Yale School of Medicine, New Haven, CT. Electronic address: tobias.carling@yale.edu.
Karolinska Institutet · SEKarolinska University Hospital · SE

Funding

Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI DAVID L RIMM · 1985 to 2026
$85.0M
NCI NIH HHS P30 CA016359
6 · The paper itself

Abstract

backgroundCytochrome P450-mediated metabolism of chemotherapeutic agents contributes to chemotherapy resistance in multiple malignancies. Adrenocortical carcinoma is known to have a poor response to adjuvant therapies; however, the mechanism remains unknown. Recent comprehensive genetic analyses of adrenocortical carcinomas demonstrated recurrent copy number gains in multiple cytochrome P450 genes prompting investigation into whether cytochrome P450 overexpression potentiates adrenocortical carcinoma chemoresistance.

methodsWe determined the expression patterns of 6 cytochrome P450 genes (CYP2A6, CYP2A7, CYP2A13, CYP2B6, CYP2S1, and CYP4F2) predicted to be amplified in adrenocortical carcinoma (n = 29) relative to normal adrenal cortex (n = 10). Gene copy numbers were determined with the TaqMan copy number assay. Gene silencing was performed via small interfering RNA (siRNA) in the adrenocortical carcinoma cell line NCI-H295R and treated with mitotane and cisplatin.

resultsOf the 6 cytochrome P450 genes tested, CYP2A6 was overexpressed with a 55-fold mean increase compared to normal adrenal samples (P < .05). Immunohistochemical analysis confirmed protein overexpression. Copy gains of CYP2A6 were found in 26% (7/27) of adrenocortical carcinoma specimens. Silencing of CYP2A6 in NCI-H295R cells resulted in decreased cell viability and increased chemosensitivity (P < .05).

conclusionFrequent upregulation in adrenocortical carcinomas and the reversal of chemoresistance in adrenocortical carcinoma cells via enforced silencing suggest a role for CYP2A6 in adrenocortical malignancy.

Indexed as

Gene Expression Regulation, NeoplasticAdrenal Cortex NeoplasmsAdrenocortical CarcinomaAgedAnalysis of VarianceAntineoplastic AgentsBiopsy, NeedleCytochrome P-450 CYP2A6Cytochrome P-450 Enzyme SystemFemaleHumansImmunohistochemistryMaleMiddle AgedMolecular Targeted TherapyPrognosisAntineoplastic AgentsCYP2A6 protein, humanCytochrome P-450 CYP2A6Cytochrome P-450 Enzyme System

Identifiers

PMID28073588
PMCPMC7301492
OpenAlexW2571024110

What OpenQuestion holds

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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.