Evidence map›Paper›PMID 37904250›Full record

ArticleBreast cancer research : BCR2023

mTOR inhibition abrogates human mammary stem cells and early breast cancer progression markers.

Hakim Bouamar, Larry Esteban Broome, Kate Ida Lathrop, Ismail Jatoi, Andrew Jacob Brenner, Alia Nazarullah, Karla Moncada Gorena, Michael Garcia, Yidong Chen, Virginia Kaklamani and 1 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Breast cancer research : BCR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02642094 (Aging Mammary Stem Cells and Breast Cancer Prevention), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.4field-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.

NCT02642094 phase2terminatednot on this map

Aging Mammary Stem Cells and Breast Cancer Prevention

TypeinterventionalSponsorLuZhe SunRan2016 to 2022Enrolled58ConditionsCancer of BreastArmsRapamycin
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Epigenetic and Immune Mechanisms Linking Breastfeeding to Lower Breast Cancer Rates.Medical science monitor : international medical journal of experimental and clinical research · 2024
    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

11 authors at 1 institution in 1 country.

Hakim Bouamar *Department of Cell Systems and Anatomy, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Larry Esteban Broome *Department of Cell Systems and Anatomy, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Kate Ida Lathrop *Department of Medicine, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Ismail JatoiDepartment of Surgery, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Andrew Jacob BrennerDepartment of Medicine, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Alia NazarullahDepartment of Pathology, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Karla Moncada GorenaFlow Cytometry Core Facility, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Michael GarciaDepartment of Medicine, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Yidong ChenDepartment of Population Health Sciences, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Virginia KaklamaniDepartment of Medicine, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. kaklamani@uthscsa.edu.
Lu-Zhe SunDepartment of Cell Systems and Anatomy, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. sunl@uthscsa.edu.
The University of Texas Health Science Center at San Antonio · US

Funding

TISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Robin Jean Leach · 1991 to 2026
$59.1M
Recruiting and Retaining URM StudentsR25GM095480 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI OYAJOBI, BABATUNDE OLUKAYODE, WEISS, DAVID S · 2011 to 2021
$3.4M
Aging mammary stem cells and breast cancer preventionR01CA192564 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI SUN, LUZHE · 2015 to 2019
$2.0M
NCI NIH HHS P30 CA054174NCI NIH HHS R01 CA192564NIGMS NIH HHS R25 GM095480
6 · The paper itself

Abstract

backgroundMammary physiology is distinguished in containing adult stem/progenitor cells that are actively amending the breast tissue throughout the reproductive lifespan of women. Despite their importance in both mammary gland development, physiological maintenance, and reproduction, the exact role of mammary stem/progenitor cells in mammary tumorigenesis has not been fully elucidated in humans or animal models. The implications of modulating adult stem/progenitor cells in women could lead to a better understanding of not only their function, but also toward possible breast cancer prevention led us to evaluate the efficacy of rapamycin in reducing mammary stem/progenitor cell activity and malignant progression markers.

methodsWe analyzed a large number of human breast tissues for their basal and luminal cell composition with flow cytometry and their stem and progenitor cell function with sphere formation assay with respect to age and menopausal status in connection with a clinical study (NCT02642094) involving a low-dose (2 mg/day) and short-term (5-7 days) treatment of the mTOR inhibitor sirolimus. The expression of biomarkers in biopsies and surgical breast samples were measured with quantitative analysis of immunohistochemistry.

resultsSirolimus treatment significantly abrogated mammary stem cell activity, particularly in postmenopausal patients. It did not affect the frequency of luminal progenitors but decreased their self-renewal capacity. While sirolimus had no effect on basal cell population, it decreased luminal cell population, particularly in postmenopausal patients. It also significantly diminished prognostic biomarkers associated with breast cancer progression from ductal carcinoma in situ to invasive breast cancer including p16INK4A, COX-2, and Ki67, as well as markers of the senescence-associated secretary phenotype, thereby possibly functioning in preventing early breast cancer progression.

conclusionOverall, these findings indicate a link from mTOR signaling to mammary stem and progenitor cell activity and cancer progression. Trial registration This study involves a clinical trial registered under the ClinicalTrials.gov identifier NCT02642094 registered December 30, 2015.

Indexed as

Breast NeoplasmsAnimalsBiomarkersEpithelial CellsFemaleHumansMammary Glands, AnimalSirolimusStem CellsTOR Serine-Threonine KinasesBiomarkersSirolimusTOR Serine-Threonine KinasesMammary stem cellsmTORProgression markersRapamycinSirolimusStem cells

Identifiers

PMID37904250
PMCPMC10614399
OpenAlexW4388023782

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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.