Evidence map›Paper›PMID 35414426›Full record

ArticleGynecologic oncology2022

Aging accelerates while multiparity delays tumorigenesis in mouse models of high-grade serous carcinoma.

Xiaoman Hou, Yali Zhai, Kevin Hu, Chia-Jen Liu, Aaron Udager, Celeste L Pearce, Eric R Fearon, Kathleen R Cho

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

Article in Gynecologic oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 16% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Molecular Management of High-Grade Serous Ovarian Carcinoma.International journal of molecular sciences · 2022
    Review
  10. The senescence-associated secretory phenotype in ovarian cancer dissemination.American journal of physiology. Cell physiology · 2022
    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

8 authors at 2 institutions in 2 countries.

Xiaoman HouDepartments of Pathology, University of Michigan Medical School, USA; Obstetrics and Gynecology Hospital, Fudan University, Shanghai, PR China.
Yali ZhaiDepartments of Pathology, University of Michigan Medical School, USA.
Kevin HuDepartments of Computational Medicine and Bioinformatics, University of Michigan Medical School, USA.
Chia-Jen LiuDepartments of Pathology, University of Michigan Medical School, USA.
Aaron UdagerDepartments of Pathology, University of Michigan Medical School, USA.
Celeste L PearceDepartments of Epidemiology Department, University of Michigan School of Public Health, USA.
Eric R FearonDepartments of Pathology, University of Michigan Medical School, USA; Departments of Internal Medicine, University of Michigan Medical School, USA; Departments of Human Genetics, University of Michigan Medical School, USA.
Kathleen R ChoDepartments of Pathology, University of Michigan Medical School, USA; Departments of Internal Medicine, University of Michigan Medical School, USA. Electronic address: kathcho@umich.edu.
University of Michigan–Ann Arbor · USObstetrics and Gynecology Hospital of Fudan University · CN

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2M
Modeling Factors Associated with Risk of High-Grade Serous Carcinoma in MiceR01CA226756 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHO, KATHLEEN R. · 2019 to 2023
$2.6M
NCI NIH HHS P30 CA046592NCI NIH HHS R01 CA226756
6 · The paper itself

Abstract

objectivesThe "incessant ovulation" hypothesis links increased risk for tubo-ovarian high-grade serous carcinoma (HGSC) due to more ovulations and reduced risk conferred by pre-menopausal exposures like oral contraceptive use, multiparity, and breastfeeding. However, most women diagnosed with HGSC are postmenopausal, implying age is a major risk factor for HGSC. Our mouse model for HGSC, based on tamoxifen (TAM)-induced somatic inactivation of the Brca1, Trp53, Rb1, and Nf1 (BPRN) tumor suppressor genes in oviductal epithelium, recapitulates key genetic, histopathologic, and biological features of human HGSCs. We aimed to credential the model for future efforts to define biological and risk modification factors in HGSC pathogenesis.

methodsBPRN mice were treated with TAM to induce tumors at defined ages and parity status.

resultsBPRN mice aged 9-months prior to tumor induction had markedly shorter survival than 6-8 week old mice induced to form tumors (median 46.5 weeks versus 61.5 weeks, log-rank test P = 0.0006). No significant differences in cancer phenotypes were observed between multiparous versus nulliparous BPRN mice. However, using a modified tumor model with one wild-type Nf1 allele (BPRN

conclusionsOur findings show aging is associated with significantly shortened survival post tumor induction in the BRPN model and multiparity delays development and/or progression of HGSC in certain genetic contexts. The findings support relevance of our mouse model to gain mechanistic insights into how known factors exert their protective effects and to test novel approaches for HGSC prevention.

Indexed as

CarcinomaCystadenocarcinoma, SerousOvarian NeoplasmsAgingAnimalsCell Transformation, NeoplasticDisease Models, AnimalFemaleHumansMiceParityPregnancyGenetically engineered mouse modelHigh-grade serous carcinomaIncessant ovulation hypothesisOvarian cancer

Identifiers

PMID35414426
PMCPMC9533776
OpenAlexW4223542903

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.