Evidence map›Paper›PMID 25892683›Full record

ArticleThe American journal of pathology2015

Profiles of cancer stem cell subpopulations in cholangiocarcinomas.

Vincenzo Cardinale, Anastasia Renzi, Guido Carpino, Alessia Torrice, Maria C Bragazzi, Felice Giuliante, Agostino M DeRose, Alice Fraveto, Paolo Onori, Chiara Napoletano and 9 more

Open access · greenAbstract read
In one paragraph

Article in The American journal of pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
7.7field-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

73 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.

  1. Guideline
  2. Article
  3. Article
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  5. Review
  6. State-of-the-Art Liver Cancer Organoids: Modeling Cancer Stem Cell Heterogeneity for Personalized Treatment.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025
    Review
  7. Article
  8. Article
  9. Review
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  12. A Novel Approach to Quantify Heterogeneity of Intrahepatic Cholangiocarcinoma: The Hidden-Genome Classifier.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
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  15. Article
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13 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

19 authors at 5 institutions in 2 countries.

Vincenzo CardinaleDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
Anastasia RenziDepartment of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
Guido CarpinoMovement, Human and Health Sciences, Division of Health Sciences, University of Rome "Foro Italico," Rome, Italy.
Alessia TorriceDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
Maria C BragazziDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
Felice GiulianteSurgery, Hepatobiliary Unit, Catholic University of the Sacred Heart School of Medicine, Rome, Italy.
Agostino M DeRoseSurgery, Hepatobiliary Unit, Catholic University of the Sacred Heart School of Medicine, Rome, Italy.
Alice FravetoDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
Paolo OnoriDepartment of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
Chiara NapoletanoDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Antonio FranchittoDepartment of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy; Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy.
Alfredo CantaforaDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
GianLuca GraziHepato-Biliary Surgery, Regina Elena National Cancer Institute, Rome, Italy.
Nicola CaporasoGastroenterology Unit, Department of Clinical and Experimental Medicine, Federico II University of Naples, Naples, Italy.
Giuseppe D'ArgenioGastroenterology Unit, Department of Clinical and Experimental Medicine, Federico II University of Naples, Naples, Italy.
Gianfranco AlpiniCentral Texas Veterans Health Care System, Scott & White Digestive Disease Research Center, Department of Medicine, Division Gastroenterology, Scott & White Healthcare and Texas A&M System Health Science Center, College of Medicine, Temple, Texas.
Lola M ReidDepartment of Cell Biology and Physiology, Program in Molecular Biology and Biotechnology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Eugenio GaudioDepartment of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
Domenico AlvaroDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy; Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy. Electronic address: domenico.alvaro@uniroma1.it.
Sapienza University of Rome · ITUniversità Cattolica del Sacro Cuore · ITBaylor Scott & White Health · USForo Italico University of Rome · ITUniversity of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
GROWTH REGULATION OF THE INTRAHEPATIC BILIARY TREER01DK054811 · NIDDK · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI ALPINI, GIANFRANCO D, GLASER, SHANNON STROUD · 2000 to 2021
$3.8M
Regulation of Bile Duct Growth in Bile Duct Ligated RatsR01DK062975 · NIDDK · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI ALPINI, GIANFRANCO D, GLASER, SHANNON STROUD · 2005 to 2014
$1.9M
TOWARD THE OPTIMAL TIMING OF INITIATION OF DIALYSISR01DK058411 · NIDDK · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI CHERTOW, GLENN MATTHEW · 2001 to 2003
$1.8M
Development of 3D organ-specific models of colorectal cancer metastasisR21CA182322 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WANG, ANDREW ZHUANG · 2013 to 2015
$644k
Autocrine/Paracrine Regulation of Intrahepatic Bile Duct GrowthI01BX000574 · VA · RLR VA MEDICAL CENTER · PI ALPINI, GIANFRANCO D · 2009 to 2022
–
BLRD VA I01 BX000574NCI NIH HHS 1R21CA182322-01NCI NIH HHS CA016086NCI NIH HHS P30 CA016086NCI NIH HHS R21 CA182322NIDDK NIH HHS DK062975NIDDK NIH HHS DK58411NIDDK NIH HHS R01 DK054811NIDDK NIH HHS R01 DK058411NIDDK NIH HHS R01 DK062975
6 · The paper itself

Abstract

Cholangiocarcinomas (CCAs) comprise a mucin-secreting form, intrahepatic or perihilar, and a mixed form located peripherally. We characterized cancer stem cells (CSCs) in CCA subtypes and evaluated their cancerogenic potential. CSC markers were investigated in 25 human CCAs in primary cultures and established cell lines. Tumorigenic potential was evaluated in vitro or in xenografted mice after s.c. or intrahepatic injection in normal and cirrhotic (carbon tetrachloride-induced) mice. CSCs comprised more than 30% of the tumor mass. Although the CSC profile was similar between mucin-intrahepatic and mucin-perihilar subtypes, CD13(+) CSCs characterized mixed-intrahepatic, whereas LGR5(+) characterized mucin-CCA subtypes. Many neoplastic cells expressed epithelial-mesenchymal transition markers and coexpressed mesenchymal and epithelial markers. In primary cultures, epithelial-mesenchymal transition markers, mesenchymal markers (vimentin, CD90), and CD13 largely predominated over epithelial markers (CD133, EpCAM, and LGR5). In vitro, CSCs expressing epithelial markers formed a higher number of spheroids than CD13(+) or CD90(+) CSCs. In s.c. tumor xenografts, tumors dominated by stromal markers were formed primarily by CD90(+) and CD13(+) cells. By contrast, in intrahepatic xenografts in cirrhotic livers, tumors were dominated by epithelial traits reproducing the original human CCAs. In conclusion, CSCs were rich in human CCAs, implicating CCAs as stem cell-based diseases. CSC subpopulations generate different types of cancers depending on the microenvironment. Remarkably, CSCs reproduce the original human CCAs when injected into cirrhotic livers.

Indexed as

AgedAged, 80 and overAnimalsBile Duct NeoplasmsBiomarkers, TumorCell Line, TumorCholangiocarcinomaEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHumansLiverMaleMiceMiddle AgedNeoplastic Stem CellsBiomarkers, Tumor

Identifiers

PMID25892683
PMCPMC4450332
OpenAlexW1982449570

What OpenQuestion holds

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Registered trials

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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.